Peptidoglycan hydrolases with bactericidal activity

Abstract

The present invention is generally in the fields of pharmaceuticals, in particular antibacterials, and protein engineering. In particular, the present invention relates to peptidoglycan hydrolases such as endolysins and nucleic acids, e.g., RNAs, encoding the peptidoglycan hydrolases of the invention, as well as medical uses thereof, for example, for treating diseases caused by and / or associated with a Staphylococcus (e.g., S. aureus) infection. Furthermore, the present invention relates to solidified yeast culture media for screening yeast cells for the secretion of peptidoglycan hydrolases with bactericidal activity and corresponding screening methods.

Description

[0001]New PCT application BioNTech SE Vossius ref.: AF3920 PCT S3 Peptidoglycan hydrolases with bactericidal activity Field of the invention The present invention is generally in the fields of pharmaceuticals, in particular antibacterials, and protein engineering. In particular, the present invention relates to peptidoglycan hydrolases such as endolysins and nucleic acids, e.g., RNAs, encoding the peptidoglycan hydrolases of the invention, as well as medical uses thereof, for example, for treating diseases caused by and / or associated with a Staphylococcus (e.g., S. aureus) infection. Furthermore, the present invention relates to solidified yeast culture media for screening yeast cells for the secretion of peptidoglycan hydrolases with bactericidal activity and corresponding screening methods. Background Staphylococci, in particular Staphylococcus aureus strains, are major human pathogens responsible for a vast array of pathologies, both acute and chronic, varying from mild to life threatening, including skin and soft tissue infections, bone-related infections, pneumonia, and sepsis. For example, S. aureus is a leading cause of mortality among antibiotic resistant bacterial pathogens, with ~ 700.000 deaths per year due to antibiotic resistant S. aureus globally; Antimicrobial Resistance Collaborators (2022), The Lancet, 399. The pathogenesis of S. aureus infection involves several critical steps: invasion of host tissues, evasion of the immune system, adhesion to surfaces, and biofilm formation. For example, by persisting in biofilm, bacteria evade neutrophil killing and display decreased susceptibility to antibiotics. Despite decades of research and promising preclinical data, there is no available vaccine against S. aureus. Peptidoglycan hydrolases (belonging to the class of “enzybiotics”) such as bacteriophage-encoded endolysins, are a promising alternative to antibiotics; Fischetti (2010), International Journal of Medical Microbiology, 300(6); Schmelcher (2012), Future Microbiology, 7; Hojckova (2013), BMC Microbiol. 13. Bacteriophages produce these enzymes, in particular endolysins, towards the end of the lytic cycle. The enzymes cleave peptidoglycans (PG) in the bacterial cell wall, thus lysing the cells and releasing the progeny phages. Peptidoglycan hydrolases, in particular endolysins (also abbreviated as “lysins”), have several advantages over antibiotics; especially, their narrow host specificity, which is often limited to a single genus or even a single species (Fischetti (2010), International Journal of Medical Microbiology, 300(6)), and their rather low propensity for generating resistance in their hosts (Schuch (2014), The Journal of Infectious Diseases 209(9)). Bacteriophages that invade Gram-positive bacteria encode a variety of highly diverse endolysins. Typically, endolysins have a modular structure consisting of one or more enzymatically active domains (EADs) connected by a flexible interdomain linker to at least one cell wall-binding domain (CBD). Both domains may contribute to the specificity for a given genus or species of bacteria; Oliveira (2013), J. Virol. 87. However, bacteriophage derived endolysins containing solely an enzymatically active domain, e.g., a cysteine, histidine-dependent amidohydrolase / peptidase (CHAP) domain (but no separate CBD), also exist. Such lysins break down peptidoglycan, in particular, from outside the bacterial cell. A native (i.e. natural) phage lysin targeting S. aureus, CF-301 (ContraFect, also known as exebacase), delivered intravenously, showed therapeutic benefit in methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections in a phase II clinical study (Fowler (2020), J. Clin. Invest., 130(7)), but the results could not be recapitulated in a phase III clinical study. Another native endolysin, SAL200, administrated intravenously to patients with persistent S. aureus bacteremia in a Phase II clinical study, resulted in serious adverse effects including pneumonia and respiratory failure (NCT03089697; Danis-Wlodarczyk (2021), Antibiotics, 10(12)); moreover, a very short half-life and an immune response against the enzyme was believed to limit its usefulness (WHO technical document, January 15, 2022: 2019 antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline, https: / / www.who.int / publications / i / item / 9789240000193). On the other hand, certain peptidoglycan hydrolases delivered locally (intranasally and / or topically) have shown some success in S. aureus decolonization, e.g. ectolysin P128 and endolysin SA.100 (Danis-Wlodarczyk (2021), Antibiotics, 10(12)) as well as lysostaphin (Jayakumar (2020), J. Appl. Microbiol.)). Exposure of S. aureus to lysostaphin, a glycylglycine endopeptidase, was however shown to generate rapid resistance both in vitro and in vivo, due to loss of function mutations in femA, which is required for the incorporation of the second and third glycine in the cross-bridges (Climo (2001), Antimicrobial Agents and Chemotherapy, 45 (5). In view of the caveats of native phage endolysins, it has been tried to improve drug-like properties of endolysins by protein engineering; De Maesschalck V (2020) Crit Rev Microbiol, 46(5). The modular architecture of endolysins has served as a basis for lysin engineering, via domain shuffling, truncation, as well as random and / or site-directed mutagenesis; Gerstmans (2020), Sci Adv. 6(23). So far, lysin optimization focused on optimizing either functional activity (Gerstmans (2020), Sci Adv.6(23)) or stability (Ritter (2019), Appl Environ Microbiol., 85(10)). Moreover, for the latter, only marginal improvements have been achieved, i.e., 4°C increase in melting temperatures for the best engineered variants. Hence, there is a need for improved antibacterials, in particular peptidoglycan hydrolases with improved pharmaceutical properties, as well as improved means and methods for generating the same. Summary of the invention Accordingly, the present invention relates to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a cysteine, histidine-dependent amidohydrolase / peptidase (CHAP) domain that has (i) a sequence identity of at least 60% to the amino acid sequence from position 72 to position 215 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions as compared to the amino acid sequence from position 72 to position 215 in SEQ ID NO: 1. As further described below, said CHAP domain is considered herein and in context of the present invention as a variant of the CHAP domain of L0482, i.e., a variant of the sequence from position 72 to position 215 in SEQ ID NO: 1. Preferably, the peptidoglycan hydrolase of the present invention has a killing activity against a Staphylococcus species or strain, preferably Staphylococcus aureus. Furthermore, the peptidoglycan hydrolase of the invention has preferably the ability of being secreted from a eukaryotic cell. Furthermore, the peptidoglycan hydrolase of the invention is, preferably, stable up to a temperature of at least about 40°C, e.g., at least 37°C. Furthermore, the peptidoglycan hydrolase of the present invention is, preferably, an endolysin. In context of the present invention, the peptidoglycan hydrolase of the invention is, preferably, contained in a pharmaceutical composition and / or, preferably, used for the treatment of a disease. Herein and in context of the present invention, the disease is, in particular, a bacterial disease, preferably, a disease caused by and / or associated with a Staphylococcus infection, e.g., a S. aureus infection. Selection of the LYSM-CHAP domain architecture as starting point for further protein engineering and directed evolution The invention is, partly, based on the surprising finding, as illustrated in the appended Examples, that lysins with a LYSM-CHAP domain architecture such as L0482 (SEQ ID NO: 1) reliably have a good killing activity against Staphylococci, in particular Staphylococcus aureus (S. aureus) including methicillin-resistant Staphylococcus aureus (MRSA) strains such as ATCC43300. Therefore, lysins with a LYSM-CHAP domain architecture such as L0482 provide a particularly good starting point for protein engineering and directed evolution approaches. In particular, it has been surprisingly found in context of the present invention that 12 out of 13 lysins with a LYSM-CHAP domain architecture (i.e., >92%) effectively killed S. aureus cells, whereas lysins with other domain architectures did often not show considerable killing activity against S. aureus; see, e.g., Example 1 and Figure 1. Moreover, it has been found that a representative of these LYSM-CHAP lysins, i.e., L0482 (SEQ ID NO: 1), had a good killing activity against many different S. aureus strains and also against other Staphylococcus species such as S. warneri and S. capitis and coagulate-negative Staphylococci such as S. epidermidis; see, e.g. Example 1 and Figure 2. Surprisingly, the killing activity against the tested Staphylococcus species and strains was even increased compared to one of the clinically most developed lysins, i.e., exebacase (also known as CF-301, ContraFect or described as “L0466” herein) which has a CHAP-SH3 domain architecture; see Figure 2. Of note, the CHAP domain of LYSM-CHAP lysins such as L0482 is very different to the CHAP domain of exebacase. In particular, the sequence identity of the CHAP domain of exebacase (i.e. the sequence from position 19 to position 164 in SEQ ID NO: 304) to the CHAP domain of L0482 (i.e. the sequence from position 72 to position 215 in SEQ ID NO: 1) is merely about 20%. Furthermore, it has been found in context of the present invention that LysM-CHAP lysins such as L0482 (SEQ ID NO: 1) can be secreted in active form by eukaryotic cells in order to kill S. aureus; see, e.g., Example 2 and Figure 3. Nevertheless, it has been also observed by the present inventors that the stability and solubility of the wild-type (WT) L0482 (SEQ ID NO: 1) and its secretion from eukaryotic cells as well as its killing activity upon secretion from eukaryotic cells is still not optimal; see, e.g., Example 4 and Figure 5, Example 5 and Figure 6, and Example 12 and Figure 10. Yet, a high killing efficiency against the target bacterium (e.g., S. aureus), a good solubility in aqueous solutions, a high stability (including a sufficient thermostability and a low tendency for aggregation) are important properties of anti-bacterial compounds, in particular, enzybiotics such as peptidoglycan hydrolases. These pharmaceutical properties are particularly important for the treatment of bacterial infections in mammals, e.g., humans, as described herein. Furthermore, administration of a peptidoglycan hydrolase in form of a nucleic acid (e.g., an mRNA) encoding the peptidoglycan hydrolase to cells in a subject (e.g., a human) has, inter alia, the advantage of continuous production, i.e., secretion, of the peptidoglycan hydrolase from the cells of the subject at the site of a bacterial infection. Hence, the ability of being efficiently secreted from eukaryotic cells, e.g., human cells, is another beneficial property of peptidoglycan hydrolases. In brief, the inventors surprisingly found that L0482 (SEQ ID NO: 1) is an optimal starting point for further protein engineering and directed evolution. Accordingly, the invention further relates to a peptidoglycan hydrolase having bactericidal activity which has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1 and which comprises one or more amino acid substitutions as compared to the sequence of SEQ ID NO: 1. This sequence identity is, in particular, calculated over the full length of the sequence of SEQ ID NO: 1 (and not over the full length of the sequence of the peptidoglycan hydrolase of the invention). Thus, any additional domains, peptides or tags that may be comprised in (or fused to) the peptidoglycan hydrolase of the invention, e.g., a signal peptide or a PK tag, should not be considered when determining the sequence identity of the peptidoglycan hydrolase of the invention to the sequence of SEQ ID NO: 1. Hence, the peptidoglycan hydrolase of the invention may comprise an amino acid sequence having a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, and, optionally, one or more further domains, peptides or tags, e.g. a signal peptide, a PK tag, a further peptide linker etc., as described herein. Preferably, the peptidoglycan hydrolase of the invention comprises a CHAP domain according to the present invention, i.e., a CHAP domain that has (i) a sequence identity of at least 60% to the amino acid sequence from position 72 to position 215 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions as compared to the amino acid sequence from position 72 to position 215 in SEQ ID NO: 1. L0482 variants with improved pharmaceutical properties (brief summary) By protein engineering, as illustrated in Example 4, and subsequent directed evolution, as illustrated in Example 5, the inventors surprisingly found L0482 variants which had several improved pharmaceutical properties at the same time. In particular, the inventors found L0482 variants which had an enhanced killing activity against S. aureus, an enhanced protein stability and an enhanced ability of being secreted from human cells, as illustrated e.g., in Example 6 and Figure 8. Enhanced killing activity As described in more detail herein below and as also illustrated in the appended Examples, an enhanced killing activity against a target bacterium such as S. aureus corresponds to a lower minimal inhibitory concentration (MIC). In particular, herein and in context of the present invention, the MIC is defined as the minimal concentration at which the optical density at 620 nm (OD620) of a bacterial (e.g. S. aureus) liquid culture comprising 5x105cfu / ml of bacterial (e.g. S. aureus) cells is kept below 0.1 for at least 24h at 37°C. Thus, the inventive peptidoglycan hydrolases provided herein may be used at a lower concentration for treating a bacterial disease than comparable peptidoglycan hydrolases, which may increase the efficiency and safety of the treatment. For example, the hit variants G1 (SEQ ID NO: 3) and H5 (SEQ ID NO: 11) found in context of the present invention have a 4- or 8-fold lower MIC than WT L0482 (SEQ ID NO: 1), respectively, i.e. a MIC of 1 µg / ml for G1 and a MIC of 0.5 µg / ml for H5, compared to a MIC of 4 µg / ml for the WT L0482; see, e.g., Figure 8. Notably, the lower MICs have been observed with the methicillin-resistant Staphylococcus aureus (MRSA) strain “ATCC43300” further highlighting that the peptidoglycan hydrolases of the invention may be particularly suitable as antibacterials, in particular, for medical uses. The enhancement of the killing activity of peptidoglycan hydrolases according to invention was further confirmed with an OD reduction assay showing that, for example, H5 (SEQ ID NO: 11) killed S. aureus cells with faster kinetics than wild-type L0482 (SEQ ID NO: 1); see, e.g., Figure 11. Enhanced protein stability An enhanced protein stability, e.g., an enhanced thermostability and / or a reduced propensity for aggregation, further improves the pharmaceutical properties of a peptidoglycan hydrolase. For example, a sufficient thermostability, in particular, the ability of being stable of up to a temperature of at least about 40°C, e.g., at least 37°C, is critical for the use as a pharmaceutical in many mammals including humans (in view of the body temperatures). Furthermore, an enhanced thermostability facilitates storage and distribution of a pharmaceutical. Thus, the inventive peptidoglycan hydrolases provided herein may be particularly suitable as pharmaceuticals. Furthermore, a decreased propensity for aggregation enhances the manufacturability of a peptidoglycan hydrolase. Thus, the inventive peptidoglycan hydrolases provided herein may be more efficiently manufactured than comparable peptidoglycan hydrolases. Moreover, a decreased propensity for aggregation further reduces the immunogenicity of a peptidoglycan hydrolase in a mammalian subject, e.g., a human, which, in turn, may further increase the efficiency and / or safety of a treatment. Enhanced ability of being secreted from human cells An enhanced ability of being secreted from human cells, is particularly important for the expression of a peptidoglycan hydrolase from a nucleic acid, e.g., a RNA. As described herein, when a suitable nucleic acid construct encoding a peptidoglycan hydrolase of the invention is introduced into cells in a subject (e.g. a human patient), said cells can continuously produce and secrete the peptidoglycan hydrolase protein. This may provide a more efficient treatment of the bacterial infection and, for example, provide a higher efficacy in treating difficult to treat bacterial infections such as bacterial biofilms. Therefore, the peptidoglycan hydrolases of the invention may be particularly suitable for delivery as a nucleic acid, e.g., a RNA. Moreover, the present invention provides more efficient means, e.g., nucleic acids encoding a peptidoglycan hydrolase of the invention, for treating bacterial infections. Enhanced solubility An enhanced stability (e.g. a reduced propensity for aggregation) and an enhanced ability of being secreted from human cells may be associated with each other as well as with an enhanced solubility in an aqueous solution such as PBS. Indeed, it has been observed in context of the present invention that many of the generated L0482 variants which were found to have an enhanced stability and an enhanced ability of being secreted from human cells also showed an enhanced solubility in PBS. Thus, the inventive peptidoglycan hydrolases provided herein may have a better solubility in aqueous solutions than comparable peptidoglycan hydrolases. This is highly beneficial, in particular, for the manufacturability and useability of the peptidoglycan hydrolases. Moreover, an enhanced solubility in aqueous solutions may increase the efficiency and / or safety of a peptidoglycan hydrolases in the treatment of a disease. Reduced propensity of generating resistance A CHAP domain (contained in L0482 and L0482 variants as described herein) may have a dual enzymatic activity, i.e., an amidase activity and a peptidase activity; Frankel (2012), J Biol Chem. 23;287(13). Both, the amidase activity and the peptidase activity, may contribute to the hydrolysis / cleavage of peptidoglycan in the cell wall of bacteria, as described herein. Therefore, a peptidoglycan hydrolase of the present invention comprising a CHAP domain of the invention may have a reduced propensity of generating resistance in target bacteria, e.g., S. aureus, compared to other peptidoglycan hydrolases such as lysostaphin. Thus, the peptidoglycan hydrolases of the invention may be particularly effective for treating bacterial infections for this additional reason. Consensus mutations / the variant H3 The inventors unexpectedly found a L0482 variant, i.e., H3 (SEQ ID NO: 9), which (i) had all of the beneficial properties assayed (i.e. an enhanced killing activity against S. aureus, an enhanced stability and an enhanced ability of being secreted from mammalian cells) compared to the parental L0482 variant L0482ag (SEQ ID NO: 2), and which (ii) contained exclusively amino acid substitutions that were deemed to be among the most beneficial ones as they were consistently observed (in slightly different combinations) among the best hits obtained by the three rounds of directed evolution, i.e., G1-G4, H1-H10 and I1-I30; see, e.g., Examples 6 and 7 and Figures 8 and 9. H3 (SEQ ID NO: 9) has been obtained by removing two glycosylation sites in L0482 (SEQ ID NO: 1) to yield the aglycosylated variant L0482ag (SEQ ID NO: 2) (see Example 4), followed by two rounds of directed evolution with L0482ag as a starting point; see Example 5. H3 (SEQ ID NO: 9) contains in addition to the two aglycosylation mutations of L0482ag, i.e. N68K, N73G, exclusively the following mutations, i.e., amino acid substitutions: T82S, N85G, R86K, S130N, H136K, D169N, N185Y and N186G, in reference to the wild-type L0482 sequence SEQ ID NO: 1. Furthermore, it has been found that several of the hit variants identified upon directed evolution of L0482ag (SEQ ID NO: 2) contained the amino acid substitution H136R instead of H136K. Hence, H136R is considered herein and in context of the present invention as a very good alternative to H136K. Thus, H3 (SEQ ID NO: 9) reflects the consensus sequence for particularly improved L0482 variants, and the corresponding amino acid substitutions, i.e. T82S, N85G, R86K, S130N, H136K / R, D169N, N185Y and N186G, in reference to the wild-type L0482 sequence SEQ ID NO: 1, are considered herein as consensus mutations, in particular, consensus amino acid substitutions. The most beneficial amino acid substitutions / the variant H5 Furthermore, it has been surprisingly found in context of the present invention that the L0482 variant H5 (SEQ ID NO: 11), obtained in the same way as H3, had an even more enhanced stability, killing activity against S. aureus, and ability of being secreted from human cells compared to H3 (SEQ ID NO: 9); see, e.g., Example 6. Surprisingly, the only difference between H5 (SEQ ID NO: 11) and H3 (SEQ ID NO: 9) was an additional amino acid substitution in H5, namely F155Y. This further demonstrates that a single amino acid substitution found in context of the present invention, e.g., F155Y, can improve several pharmaceutical properties of L0482, as described herein, at the same time. Hence, the amino acid substitutions T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1 are considered herein and in context of the present invention as the most beneficial amino acid substitutions for enhancing the killing activity against a target bacterium, e.g., S. aureus, and / or other pharmaceutical properties (e.g., the stability, solubility and secretion from human cells) of L0482 derived peptidoglycan hydrolases (L0482 variants). Moreover, it needs to be emphasized that it has been surprisingly found in context of the present invention that all of the most beneficial amino acid substitutions occurred in the CHAP domain of L0482, i.e., positions 72 to 215 in SEQ ID NO: 1. It is therefore considered herein and in context of the present invention that the CHAP domain is the most important domain of L0482 derived peptidoglycan hydrolases. Hence, the present invention further relates, in particular, to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1 and that has (ii) one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. Preferably, said CHAP domain further comprises an aglycosylation mutation as described herein, i.e., an amino acid substitution or deletion, preferably an amino acid substitution, at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is, preferably, substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably glycine. The surprising finding of L0482 variants (e.g., H3 and H5), wherein several pharmaceutical properties were improved at the same time, is partly based on the improved means and method for protein engineering and directed evolution developed in context of the present invention and described herein. Means and methods for screening peptidoglycan hydrolases for bactericidal activity As illustrated in the appended Examples, the inventors surprisingly found that solidified yeast culture media such as agar plates containing autoclaved (i.e. dead) target bacteria, e.g. dead S. aureus cells, are particularly suitable for screening yeast cells for the secretion of an active peptidoglycan hydrolase, i.e., for identifying peptidoglycan hydrolases with a good killing activity against target bacteria, e.g., S. aureus. The corresponding screening method called “Yeast on dead aureus” (YODA) is based on the inventive concept that only an active (but not an inactive) peptidoglycan hydrolase secreted from a yeast colony cultured on the solidified yeast culture medium of the invention is able to break down the peptidoglycan of the dead bacterial cells in vicinity of the colony. Hence, only a secreted and active peptidoglycan hydrolase renders the previously turbid culture medium locally translucent and thereby generates a halo around the colony secreting said peptidoglycan hydrolase; see Example 3 and Figure 4. YODA-derived methods are extremely simple and efficient methods which allows to easily distinguish yeast cells / colonies expressing peptidoglycan hydrolases with a good killing activity against a target bacterium from yeast cells / colonies expressing inactive peptidoglycan hydrolases. Furthermore, YODA-derived methods are very sensitive since the lysins are constantly secreted from the cells. Thus, small secretion rates may be sufficient to see a halo (when the peptidoglycan hydrolase is active). Moreover, as described herein, e.g., in Example 3, the YODA method or derivatives thereof as described herein (e.g., YODB) have additional advantages over prior art screening methods, e.g., the double agar layer (DAL) assay described in Zhao (2014). Appl Environ Microbiol 80(9). Accordingly, the present invention further relates to a solidified yeast culture medium comprising substrate particles intermixed with said medium, wherein said substrate particles comprise dead bacterial cells and / or fragments thereof, and / or peptidoglycan particles. Furthermore, the invention relates to a method of screening yeast cells for the secretion of an active peptidoglycan hydrolase (i.e., a peptidoglycan hydrolase with bactericidal activity against a target bacterium, e.g., S. aureus), said method comprising the steps of: a) providing a solidified yeast culture medium comprising substrate particles intermixed with said medium, wherein said substrate particles comprise dead bacterial cells and / or fragments thereof, and / or peptidoglycan particles; b) culturing yeast cells expressing a peptidoglycan hydrolase on a surface of said solidified medium until at least one yeast colony is detectable, in particular wherein the yeast cells are able to secrete the peptidoglycan hydrolase; c) evaluating whether a halo is apparent around a yeast colony, in particular wherein the halo corresponds to a locally reduced optical density of said solidified medium around said colony, for example, in a radius of about 0.1 to 1 cm from the colony, especially compared to a region of the solidified medium that is free of yeast colonies; d) determining that a yeast colony secretes an active peptidoglycan hydrolase when a halo around the colony is apparent, or determining that a yeast colony does not secrete an active peptidoglycan hydrolase when no halo around the colony is apparent. As illustrated in the appended Examples, the inventive YODA-derived screening method provided herein has been proven very useful for identifying improved peptidoglycan hydrolases with bactericidal activity, e.g., against S. aureus; see, e.g., Examples 4 to 6. Aglycosylation mutations enhance bactericidal activity upon expression in eukaryotic cells As shown in Example 4 and Figure 5A, it has been found in context of the present invention that WT L0482 (SEQ ID NO: 1) has a good killing activity against S. aureus, i.e., a minimum inhibitory concentration (MIC) of 4 µg / ml, when produced in Escherichia coli (E. coli) but only a moderate killing activity (i.e. a MIC of 352 µg / ml when secreted from Pichia pastoris (P. pastoris), i.e., yeast. The inventors reasoned that N-and O-glycosylation of WT L0482 during its maturation in the secretory pathway in eukaryotic cells might have negatively affected its bactericidal activity. In particular, the inventors speculated that transgenes such as lysins may be glycosylated at sites essential for folding and activity, which could potentially lead to the secretion of a less active protein (while secretory proteins are normally evolutionary adapted to these modifications). It has been found that L0482 (SEQ ID NO: 1) contains two motifs of N-glycosylation at residues N68 (which is in the linker sequence) and N73 (which is in the CHAP domain). Therefore, the inventors removed the two N- glycosylation motifs in L0482 in a degenerate codon screen by employing the YODA method as described in Example 4 and Figure 5B. The inventors surprisingly found that the most frequent amino acid substitution pairs contained in active L0482 mutants were N68K / N73G (i.e. N68N73 to KG), N68K / N73Y (i.e. N68N73 to KY), and N68A / N73H (i.e. N68N73 to AH). It was confirmed that all three L0482 mutants (i.e., having the N68K / N73G, N68K / N73Y and N68A / N73H substitutions, respectively) were aglycosylated; see, e.g., Example 4 and Figure 5C. In addition, the further mutation pairs N68N73 to ML, RE, KL and AA were also found in active L0482 mutants by YODA. Moreover, it has been surprisingly found by the inventors that the aglycosylated N68K / N73G (i.e., KG) mutant, also called L0482ag herein, had a killing activity against S. aureus which was almost as good as for the WT L0482 upon production in E. coli; see, e.g., Example 4 and Figure 5C. Accordingly, the present invention further relates to aglycosylated variants of L0482 (SEQ ID NO: 1) as illustrated by but not limited to the N68K / N73G (i.e., L0482ag; SEQ ID NO: 2) mutant described herein. Herein and in context of the invention, e.g., in the context of a peptidoglycan hydrolase that has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, an aglycosylation mutation refers to an amino acid substitution or deletion (preferably to an amino acid substitution) at position 68 or 73 in SEQ ID NO: 1 or at any position corresponding to these positions. In context of the CHAP domain of the invention, an aglycosylation mutation refers to an amino acid substitution or deletion (preferably to an amino acid substitution) at position 73 in SEQ ID NO: 1 or at a position corresponding to this position. In particular, an amino acid substitution at position 68 in SEQ ID NO: 1 or at a position corresponding to this position means that the asparagine (“N”) at position 68 in SEQ ID NO: 1 is substituted with another amino acid, as described herein. Following the same logic, an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position means that the asparagine (“N”) at position 73 in SEQ ID NO: 1 or the asparagine corresponding to position 73 in SEQ ID NO: 1 is substituted with another amino acid, as described herein. The following amino acid substitutions are considered herein and in context of the present invention as particularly effective aglycosylation mutations or aglycosylation amino acid substitutions: N68K, N68A, N68M, N68R, N73G, N73Y, N73H, N73L, N73E, and N73A in SEQ ID NO: 1 or at positions corresponding to these positions. Since the CHAP domain is of most relevance herein and in context of the present invention, an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, e.g. N73G (as contained in L0482ag; SEQ ID NO: 2), is of particular relevance herein and in context of the present invention. L0482 variants having at least one aglycosylation mutation (e.g., an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position), as described herein and as illustrated by L0482ag (SEQ ID NO: 2), may be a particularly good starting point for further protein engineering and / or directed evolution, as described herein. As illustrated in the appended Examples, and as further described herein, additional permissive, beneficial, particularly beneficial or most beneficial amino acid substitutions may be introduced into L0482 variants having at least one aglycosylation mutation, in particular in the CHAP domain thereof, to further enhance the pharmaceutical properties of the L0482 variants (e.g. the stability solubility and ability of being secreted from a human cell but also the killing activity against a target bacterium, e.g. S. aureus), as described herein. Thus, an aglycosylation mutation (preferably an amino acid substitution) at position 73 in SEQ ID NO: 1 or at a position corresponding to this position (more preferably N73G), is, preferably, combined with at least one of the amino acid substitutions described herein in context of the L0482ag variants obtained upon directed evolution, in particular with at least one permissive or beneficial amino acid substitution, preferably with at least one particularly beneficial amino acid substitution, more preferably with at least one of the most beneficial amino acid substitutions, as further described herein, i.e., more preferably with at least one of the amino acid substitutions selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in reference to SEQ ID NO: 1. Hence, the present invention further relates, in particular, to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1 and that has (ii) an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position. Preferably, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with another amino acid residue than phenylalanine or lysine such as glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably glycine. In addition, the present invention relates to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase has (i) a sequence identity of at least 60% to the sequence of SEQ ID NO: 1 and has (ii) at least one amino acid substitution at positions 68 and 73 in SEQ ID NO: 1 or at positions corresponding to these positions, preferably at least at position 73 in SEQ ID NO: 1 or at a position corresponding to this position. Preferably, the residue at position 68 (i.e. the “N”) in SEQ ID NO: 1 or at a position corresponding to this position is substituted with another amino acid residue than threonine or serine such as lysine, methionine, arginine or alanine, preferably lysine. Furthermore, the residue at position 73 (i.e. the “N”) in SEQ ID NO: 1 or at a position corresponding to this position is preferably substituted with another amino acid residue than phenylalanine or lysine such as glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably glycine. Preferably, said peptidoglycan hydrolase comprises a CHAP domain according to the present invention. Methods for screening peptidoglycan hydrolases having several improved pharmaceutical properties / directed evolution As already indicated herein above, the inventors evaluated in context of the present invention whether it would be possible to not only improve the bactericidal activity of lysins but also further pharmaceutical properties of the lysins at the same time, (e.g., the solubility, secretion from eukaryotic cells and / or stability). As already indicated above and as further described in the following, the inventors surprisingly found that several pharmaceutical properties (including the bactericidal activity) of L0482 variants, in particular L0482ag, could be further improved. To this end, the inventors developed a combinatorial screening method based on the inventive YODA-derived method which combines eukaryotic cell display, e.g. yeast display, with YODA; see, e.g., Example 5. As illustrated in the appended Examples, it has been surprisingly found that this inventive combinatorial screening method, allows to simultaneously improve, inter alia, the solubility, bactericidal activity and eukaryotic secretion of peptidoglycan hydrolases, e.g., endolysins such as L0482 (SEQ ID NO: 1) or derivatives thereof such as L0482ag (SEQ ID NO: 2). The inventors reasoned that the display (e.g. yeast display) step allows, in particular, to screen for peptidoglycan hydrolase variants which are adapted to the eukaryotic secretory pathway, and, hence, have an improved expression and secretion profile in eukaryotic cells. Moreover, the ability of being efficiently secreted is often associated with a good stability and good solubility of the protein, as described herein. Hence these biophysical and pharmaceutically relevant properties can be also improved by the inventive method. The YODA step, in particular, allows to screen for secreted peptidoglycan hydrolase variants which have good bactericidal activity, in particular against the desired target bacterium, as described herein. Hence, the combinatorial screening method of the invention allows to screen for improved peptidoglycan hydrolase variants which are adapted to the eukaryotic secretory pathway and effectively kill a target bacterium, e.g. S. aureus, and which may have further beneficial pharmaceutical properties such as an enhanced stability and an enhanced solubility as described herein and as illustrated in the appended Examples. As already mentioned above, the inventive YODA-based method refers to a method of screening yeast cells for the secretion of an active peptidoglycan hydrolase, said method comprising the steps of: a) providing a solidified yeast culture medium comprising substrate particles intermixed with said medium, wherein said substrate particles comprise dead bacterial cells and / or fragments thereof, and / or peptidoglycan particles; b) culturing yeast cells expressing a peptidoglycan hydrolase on a surface of said solidified medium until at least one yeast colony is detectable; c) evaluating whether a halo is apparent around a yeast colony; d) determining that a yeast colony secretes an active peptidoglycan hydrolase when a halo around the colony is apparent, or determining that a yeast colony does not secrete an active peptidoglycan hydrolase when no halo around the colony is apparent. Herein and in context of the present invention, said YODA-based method can be combined with a eukaryotic cell display method. In particular, said method of screening yeast cells for the secretion of an active peptidoglycan hydrolase may be performed in step III) of the method of identifying an active peptidoglycan hydrolase variant that is optimized for secretion by a eukaryotic cell according to the invention, in particular, as described in the following: Hence, the present invention further relates to a method of identifying an active peptidoglycan hydrolase variant (i.e., a peptidoglycan hydrolase variant with bactericidal activity against a target bacterium, e.g., S. aureus) that is optimized for secretion by a eukaryotic cell, said method comprising the steps of: I) preparing a library of eukaryotic cells, preferably yeast cells, expressing peptidoglycan hydrolase variants on the cell surface; II) selecting eukaryotic cells, e.g. yeast cells, based on a high level of peptidoglycan hydrolase on the cell surface relative to other cells in the library; for example, selecting the 10%, 5%, 1% or 0.5% of cells in the library with the highest peptidoglycan level on the cell surface; III) performing the inventive method of screening yeast cells for the secretion of an active peptidoglycan hydrolase provided herein (i.e. a YODA-derived method), wherein yeast cells that are able to secrete the peptidoglycan hydrolase variants expressed in the eukaryotic cells selected in step II) are cultured in step b) of said method of screening yeast cells for the secretion of an active peptidoglycan hydrolase; and IV) determining that a yeast colony that has been determined in step d) of said method of screening yeast cells for the secretion of an active peptidoglycan hydrolase to secrete an active peptidoglycan hydrolase produces an active peptidoglycan hydrolase variant that is optimized for secretion by a eukaryotic cell. Moreover, said method, i.e., the combinatorial screening method of the present invention, can be used for directed evolution of peptidoglycan hydrolases, e.g. endolysins, such as L0482 (SEQ ID NO: 1) or derivatives thereof, e.g., L0482ag (SEQ ID NO: 2), as illustrated in the appended Examples. Therefore, in certain embodiments, at least two rounds of steps I) to IV) of the inventive method of identifying an active peptidoglycan hydrolase variant that is optimized for secretion by a eukaryotic cell are performed, wherein in step I) of each subsequent round, a further library of eukaryotic cells is prepared, and wherein the cells in the library express a different set of peptidoglycan variants compared to the library employed in the preceding round(s). Summary of beneficial and permissive amino acid substitutions found by the aglycosylation screen or directed evolution As already indicated above and as further described herein and as illustrated in the appended Examples, the inventive screening methods provided herein contributed to finding the inventive peptidoglycan hydrolases, in particular, L0482 variants, which surprisingly had several improved pharmaceutical properties at the same time. In particular, 252 L0482 variants, especially, aglycosylated L0482 variants derived from L0482ag (SEQ ID NO: 2), have been generated in three rounds of directed evolution; see, e.g., Example 5 to 7. Importantly, all these L0482 variants had the ability of being secreted by eukaryotic cells, in particular yeast cells, and are deemed to have a killing activity against S. aureus as determined by the YODA method described in Example 3. Based on this large and very informative data set the inventors not only were able to find the most beneficial mutations described herein but many further beneficial, or at least permissive, amino acid substitutions at many positions in SEQ ID NO: 1 (or SEQ ID NO: 2) that were contained in the active and secreted L0482ag variants; see, e.g., Example 7 and Table 3. It is credible that essentially all amino acid substitutions found in active and secreted L0482ag variants are beneficial or at least permissive for the desired pharmaceutical properties of L0482 variants. In particular, it is credible that essentially all, or at least the vast majority, of these amino acid substitutions alone or in combination confer to the LYSM-CHAP lysins, in particular L0482 variants, a sufficient killing activity against Staphylococcus species or strains, in particular S. aureus, a sufficient ability of being secreted from eukaryotic cells, a sufficient stability and / or a sufficient solubility. As illustrated in the appended Examples, e.g., in Examples 4 to 7, amino acid substitutions in the CHAP domain of L0482 which may confer, enhance, or, at least, maintain (i) a killing activity against Staphylococcus species or strains, in particular S. aureus, and (ii) the ability of being secreted from eukaryotic cells, and preferably (iii) a sufficient solubility and / or stability, have been identified to occur, in particular, at positions 72 to 76, 78, 81, 82, 85, 86, 93, 96, 104, 107, 108, 111, 113, 115, 117, 121, 124, 125, 129, 130, 133 to 136, 138, 140 to 142, 144, 145, 148, 149, 152, 153, 155, 157, 159, 169, 173, 175 to 178, 185, 186, 190 to 194, 197, 198, 199, 201, 203, 204, 207, and 212 to 215 in SEQ ID NO: 1, or at positions corresponding to these positions. Accordingly, the present invention relates to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1 and that has (ii) one or more amino acid substitutions at positions 72 to 76, 78, 81, 82, 85, 86, 93, 96, 104, 107, 108, 111, 113, 115, 117, 121, 124, 125, 129, 130, 133 to 136, 138, 140 to 142, 144, 145, 148, 149, 152, 153, 155, 157, 159, 169, 173, 175 to 178, 185, 186, 190 to 194, 197, 198, 199, 201, 203, 204, 207, and 212 to 215 in SEQ ID NO: 1, or at positions corresponding to these positions, wherein the amino acid residue at position 72 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably glycine or serine, more preferably glycine, the amino acid residue at position 74 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine or proline, the amino acid residue at position 75 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine or proline, the amino acid residue at position 76 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 78 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or tyrosine, the amino acid residue at position 81 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, arginine or serine, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or methionine, preferably lysine, the amino acid residue at position 93 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or leucine, the amino acid residue at position 96 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 104 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 107 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or tyrosine, the amino acid residue at position 108 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 111 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 113 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 115 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 117 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, the amino acid residue at position 121 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 124 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine or histidine, the amino acid residue at position 125 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 129 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or serine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, isoleucine or asparagine, preferably asparagine, the amino acid residue at position 133 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or threonine, the amino acid residue at position 134 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine or valine, the amino acid residue at position 135 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine or histidine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue at position 138 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 140 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or aspartic acid, the amino acid residue at position 141 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 142 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or arginine, the amino acid residue at position 144 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 145 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or leucine, the amino acid residue at position 148 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine or valine, the amino acid residue at position 149 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or threonine, the amino acid residue at position 152 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 153 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine or serine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 157 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 159 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, asparagine or arginine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, glutamine or threonine, the amino acid residue at position 176 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or arginine, the amino acid residue at position 177 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 178 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine or arginine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, histidine, serine or tyrosine, preferably tyrosine, the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 190 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 191 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or arginine, the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or threonine, the amino acid residue at position 193 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 194 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 197 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 198 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 199 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 201 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid or serine, the amino acid residue at position 203 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid or valine, the amino acid residue at position 204 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, serine or tyrosine, the amino acid residue at position 207 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine or valine, the amino acid residue at position 212 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 213 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or threonine. the amino acid residue at position 214 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or threonine, and / or the amino acid residue at position 215 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, valine or serine. Furthermore, it is preferred that said CHAP domain has an aglycosylation substitution, i.e., an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, and in addition, at least one amino acid substitution at the other positions described herein above, i.e., at positions 72, 74 to 76, 78, 81, 82, 85, 86, 93, 96, 104, 107, 108, 111, 113, 115, 117, 121, 124, 125, 129, 130, 133 to 136, 138, 140 to 142, 144, 145, 148, 149, 152, 153, 155, 157, 159, 169, 173, 175 to 178, 185, 186, 190 to 194, 197, 198, 199, 201, 203, 204, 207, and 212 to 215 in SEQ ID NO: 1, or at positions corresponding to these positions, preferably at least one amino acid substitution at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions. Accordingly, the present invention further relates to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a cysteine, histidine-dependent amidohydrolase / peptidase (CHAP) domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1, and that has (ii) one or more amino acid substitutions at positions 72, 74 to 76, 78, 81, 82, 85, 86, 93, 96, 104, 107, 108, 111, 113, 115, 117, 121, 124, 125, 129, 130, 133 to 136, 140 to 142, 144, 145, 148, 149, 152, 153, 155, 157, 159, 169, 173, 175 to 178, 185, 186, 190 to 192, 194, 197, 198, 199, 201, 203, 204, 207, and 212 to 215 in SEQ ID NO: 1, or at positions corresponding to these positions, preferably at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, as described herein. Preferably, said CHAP domain further has an aglycosylation mutation, i.e. an amino acid substitution or deletion, preferably a substitution, at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Particularly beneficial amino acid substitutions / selected hit variants As already indicated herein above, the present inventors found several hit variants of L0482ag (SEQ ID NO: 2) upon each round of directed evolution, i.e., G1 to G4 (SEQ ID NO: 3 to 6) upon round 1, H1 to H10 (SEQ ID NO: 7 to 16) upon round 2 and I1 to I30 (SEQ ID NO: 17 to 46) upon round 3. The various amino acid substitutions contained in these hit variants (in addition to the two aglycosylation substitutions N68K and N73G) are considered herein and in context of the present invention as particularly beneficial mutations, i.e., amino acid substitutions; see, e.g., Examples 5 to 7. As illustrated in the appended Examples, particularly beneficial amino acid substitutions in the CHAP domain of L0482 which may confer, enhance, or, at least, maintain (i) a killing activity against Staphylococcus species or strains, in particular S. aureus, and (ii) the ability of being secreted from eukaryotic cells, and (iii) preferably a sufficient solubility and stability, have been identified to occur, in particular, at positions 73, 75, 78, 81, 82, 85, 86, 104, 107, 115, 124, 125, 130, 133, 135, 136, 140, 141, 155, 169, 173, 175, 178, 185, 186, 191 to 194, 198, 204, 212 and 215 in SEQ ID NO: 1 or at positions corresponding to these positions, as described herein. Accordingly, the present invention further relates to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1, and that has (ii) one or more amino acid substitutions at positions 73, 75, 78, 81, 82, 85, 86, 104, 107, 115, 124, 125, 130, 133, 135, 136, 140, 141, 155, 169, 173, 175, 178, 185, 186, 191, 192, 194, 198, 204, 212 and 215 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine or serine, preferably glycine, the amino acid residue at position 75 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 78 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 81 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 104 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 107 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 115 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 124 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 125 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 133 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 135 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue at position 140 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 141 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 178 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 191 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 194 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 198 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 204 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 212 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue at position 215 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine. Furthermore, it is preferred that said CHAP domain has an aglycosylation mutation, preferably, an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, more preferably N73G, and in addition, at least one particularly beneficial amino acid substitution at the other positions described herein above, i.e., at positions 75, 78, 81, 82, 85, 86, 104, 107, 115, 124, 125, 130, 133, 135, 136, 140, 141, 155, 169, 173, 175, 178, 185, 186, 191, 192, 194, 198, 204, 212 and 215 in SEQ ID NO: 1, or at positions corresponding to these positions, preferably at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions. Accordingly, the present invention further relates to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 2, and that has (ii) one or more amino acid substitutions at positions 75, 78, 81, 82, 85, 86, 104, 107, 115, 124, 125, 130, 133, 135, 136, 140, 141, 155, 169, 173, 175, 178, 185, 186, 191, 192, 194, 198, 204, 212 and 215 in SEQ ID NO: 1, or at positions corresponding to these positions, as described herein, preferably one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, as described herein. Most beneficial amino acid substitutions As already indicated above, based on the characterizations of the hit variants of L0482 (see, e.g., Example 6 and Figure 8) found in context of the present invention and comparative analyses of the sequences of these hits (see, e.g., Example 7), the inventors were able to find the most beneficial amino acid substitutions, i.e., T82S, N85G, R86K, S130N, H136K / R (preferably H136K), F155Y, D169N, N185Y and N186G in SEQ ID NO: 1. As mentioned above, the most beneficial amino acid substitutions refer to the only amino acid substitutions contained in the hit variant H5 (SEQ ID NO: 11) vis à vis the parental L0482ag variant (SEQ ID NO: 2); see, e.g., Figure 9A. H5 is considered herein as the variant obtained by two rounds of directed evolution with the best pharmaceutical properties. As mentioned above, the most beneficial amino acid substitutions in H5 strongly enhanced the killing activity against S. aureus including S. aureus biofilms, the protein stability and the ability of being secreted from humans cells; see, e.g., Figures 8, 9, 11 and 12. Therefore, as already mentioned above, the present invention further relates, in particular, to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1, and that has (ii) one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. Preferably, said CHAP domain has a plurality of said most beneficial amino acid substitutions (e.g., 2, 3, 4, 5, 6, 7, 8 or 9), preferably at least 6 or 7, more preferably at least 8, most preferably all of said most beneficial amino acid substitutions. Furthermore, said CHAP domain has preferably further an aglycosylation mutation, preferably an amino acid substitution, at position 73 in SEQ ID NO: 1 or at a position corresponding to this mutation as described herein, more preferably N73G. The most recurrent one of the most beneficial amino acid substitutions: R86K Furthermore, it has been surprisingly found in context of the present invention that the amino acid substitution R86K was contained in all 44 identified hit variants, i.e., G1-G4, H1-H10 and I1-I30, and in 96.08% of all L0482 variants that were secreted from eukaryotic cells and that were determined to have a killing activity against S. aureus, as described herein and as illustrated in the appended Examples; see, e.g., Example 7 and Figure 9. Therefore, R86K in SEQ ID NO: 1 is, herein and in context of the present invention, a particularly preferred amino acid substitution among the most beneficial amino acid substitutions identified. Accordingly, in particularly preferred embodiments, the CHAP domain of the present invention has an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at said position is substituted with lysine. Recurrent pairs of amino acid substitutions among the most beneficial amino acid substitutions It has been further surprisingly found in context of the present invention that certain amino acid substitutions occurred together in pairs in the identified hit variants, i.e., G1-G4, H1-H10 and I1-I30; see, e.g., Example 7 and Figure 9. These mutation pairs are specifically: (i) T82S and N85G, (ii) S130N and H136K / R and (iii) N185Y and N186G. Each of said 44 hit variants contained at least one of said mutation pairs. Of note, it is beneficial but not necessary that these amino acid substitutions, i.e., T82S and N85G, S130N and H136K / R, and N185Y and N186G, occur in pairs since among the 252 active L0482 variants secreted from yeast cells found in context of the present invention, variants having only one of these paired mutations (but not the other) were found as well. Therefore, a CHAP domain of the invention having an amino acid substitution at position 82 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, has preferably, in addition, an amino acid substitution at position 85 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Similarly, a CHAP domain of the invention having an amino acid substitution at position 85 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, has preferably, in addition, an amino acid substitution at position 82 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Furthermore, a CHAP domain of the invention having an amino acid substitution at position 130 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, has preferably, in addition, an amino acid substitution at position 136 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Similarly, a CHAP domain of the invention having an amino acid substitution at position 136 of SEQ ID NO: 1 or at a position corresponding to this position as described herein, has preferably, in addition, an amino acid substitution at position 130 of SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Furthermore, a CHAP domain of the invention having an amino acid substitution at position 185 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, has preferably, in addition, an amino acid substitution at position 186 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Similarly, a CHAP domain of the invention having an amino acid substitution at position 186 of SEQ ID NO: 1 or at a position corresponding to this position as described herein, has preferably, in addition, an amino acid substitution at position 185 of SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Consensus mutation units As already mentioned herein above, the hit variant H3 (SEQ ID NO: 9) reflects the consensus sequence for particularly improved L0482 variants. H3 contains exclusively, the following amino acid substitutions, also referred to herein as “consensus mutations”: T82S, N85G, R86K, S130N, H136K / R (esp. H136K), D169N, N185Y and N186G in reference to SEQ ID NO: 1. Furthermore, the inventors found five consensus mutation units for particularly improved L0482 variants based on the 44 L0482ag hit variants and the consensus sequence reflected by H3 (SEQ ID NO: 9) found in context of the present invention. These consensus mutation units consist of 1 or 2 amino acid substitutions, i.e.: (i) R86K (which is particularly preferred), (ii) T82S and N85G, (iii) S130N and H136K / R (preferably H136K), (iv) D169N, and (v) N185Y and N186G. Accordingly, in preferred embodiments, the CHAP domain of the present invention has at least one amino acid substitution or substitution pair ( i.e. at least one consensus mutation unit) selected from the group consisting of the following (i) to (v): (i) an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at said position is substituted with lysine; (ii) an amino acid substitution at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, and the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; (iii) an amino acid substitution at positions 130 and 136 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, and the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine; (iv) an amino acid substitution at position 169 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at said position is substituted with asparagine; and (v) an amino acid substitution at positions 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. Preferably, said CHAP domain has at least two, preferably at least three, more preferably at least four, most preferably all of said consensus mutation units. Preferably, said CHAP domain has further an aglycosylation mutation as described herein, preferably an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein, more preferably the substitution N73G. Furthermore, said CHAP domain has preferably the amino acid substitution F155Y. In certain preferred embodiments, the CHAP domain of the present invention has a sequence identity of at least 94% (in particular, at least 93.9%), at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% to the sequence from position 72 to position 215 in SEQ ID NO: 9 (H3). Preferably, said CHAP domain has a) (i) at least one of the consensus mutations or consensus mutation units described herein and (ii) at least one aglycosylation mutation, preferably an amino acid substitution at position 73 as described herein, and / or b) at least two of the consensus mutations, e.g., at least one amino acid substitution pair, as described herein. Furthermore, in context of these preferred embodiments or in similar preferred embodiments, the CHAP domain of the present invention has at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, at most 1 or no amino acid substitutions in the sequence from position 72 to position 215 in SEQ ID NO: 9 (H3) or in the sequence from a position corresponding to position 72 in SEQ ID NO: 9 to a position corresponding to position 215 in SEQ ID NO: 9. Furthermore, said CHAP domain has preferably the amino acid substitution F155Y. In certain preferred embodiments, the peptidoglycan hydrolase of the present invention has a sequence identity of at least 95% (in particular at least 95.4%), at least 96%, at least 97%, at least 98% or at least 99% to the sequence of SEQ ID NO: 9 (H3). Furthermore, in context of these preferred embodiments or in similar preferred embodiments, the peptidoglycan hydrolase of the present invention has at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, at most 1 or no amino acid substitutions in SEQ ID NO: 9. Preferably, said peptidoglycan hydrolase comprises a CHAP domain according to the present invention. A single amino acid substitution improving several pharmaceutical properties at once: F155Y As further indicated herein above, the best performing L0482 variant found and characterized in context of the present invention, i.e. H5 (SEQ ID NO: 11), surprisingly contained exclusively one additional amino acid substitution vis à vis H3 (SEQ ID NO: 9), i.e., F155Y. As further described herein, said amino acid substitution improved several pharmaceutical properties compared to H3 (SEQ ID NO: 9) at the same time, i.e. the killing activity against S. aureus, the protein stability and the ability of being secreted from human cells; see, e.g, Figure 8. Therefore, F155Y in SEQ ID NO: 1 is considered herein and in context of the present invention as a further particularly preferred amino acid substitution among the most beneficial amino acid substitutions identified. Accordingly, in particularly preferred embodiments, the CHAP domain of the present invention has an amino acid substitution at position 155 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at said position is substituted with tyrosine. Preferably, said CHAP domain further has at least one consensus mutation, as described herein, (i.e., T82S, N85G, R86K, S130N, H136K / R (preferably H136K), D169N, N185Y and / or N186G), or, more preferably, at least one consensus mutation unit, as described herein, i.e., (i) R86K (particularly preferred), (ii) T82S and N85G, (iii) S130N and H136K / R (preferably H136K), (iv) D169N, and / or (v) N185Y and N186G; and / or an aglycosylation substitution as described herein, i.e., an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein, preferably N73G. In further preferred embodiments, the CHAP domain of the present invention has a sequence identity of at least 93% (in particular, at least 93.2%), at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% to the sequence from position 72 to position 215 in SEQ ID NO: 11 (H5). Preferably, said CHAP domain has a) (i) at least one of the most beneficial amino acid substitutions and / or at least one consensus mutation unit, as described herein and (ii) at least one aglycosylation mutation, preferably an amino acid substitution at position 73, as described herein, and / or b) at least two of the most beneficial amino acid substitutions, e.g., at least one amino acid substitution pair, as described herein. Furthermore, in context of these preferred embodiments or in similar preferred embodiments, the CHAP domain of the present invention has at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, at most 1 or no amino acid substitutions in the sequence from position 72 to position 215 in SEQ ID NO: 11 (H5) or in the sequence from a position corresponding to position 72 in SEQ ID NO: 11 to a position corresponding to position 215 in SEQ ID NO: 11. In certain preferred embodiments, the peptidoglycan hydrolase of the present invention has a sequence identity of at least 95% (in particular at least 95.0%), at least 96%, at least 97%, at least 98% or at least 99% to the sequence of SEQ ID NO: 11 (H5). Furthermore, in context of these preferred embodiments or in similar preferred embodiments, the peptidoglycan hydrolase of the present invention has at most 10, at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, at most 1 or no amino acid substitutions in SEQ ID NO: 11. Preferably, said peptidoglycan hydrolase comprises a CHAP domain according to the present invention. Furthermore, the peptidoglycan hydrolase of the present invention is, in particular, a single polypeptide, i.e., a single amino acid chain. Administration in form of a nucleic acid As already indicated above, administration of a peptidoglycan hydrolase of the invention in form of a nucleic acid (e.g., an mRNA) encoding said peptidoglycan hydrolase to a subject (e.g., a human), in particular introducing the nucleic acid into cells in a subject, has certain advantages. For example, when a nucleic acid (e.g., an mRNA) encoding a peptidoglycan hydrolase of the invention is introduced and expressed in cells in a subject, e.g., in a patient that has a bacterial, e.g. Staphylococcus, infection, the cells can continuously produce and secrete the peptidoglycan hydrolase protein. This may provide a more efficient treatment of the bacterial infection and, for example, provide a higher efficacy in treating difficult to treat bacterial infections such as bacterial biofilms, e.g., Staphylococcus biofilms. Furthermore, the nucleic acid may be introduced into cells at a particular location, e.g. the site of a bacterial infection, and / or specific cell types which may further improve the efficiency and / or safety of the treatment. Furthermore, nucleic acids, in particular RNAs, have further certain practical advantages over proteins with respect to their manufacturing, safety profile and / or adaptability. It has been further found by the inventors that all hit variants found in context of the invention and further tested, i.e., G1 to G4 and H1 to H6, were efficiently secreted from human cells when expressed from an RNA in these cells. In particular, it has been found that the secretion from human cells was highly enhanced compared to a control RNA expressing WT L0482 (SEQ ID NO: 1); see Examples 11 and 12 and Figure 10. Therefore, the present invention further relates to a nucleic acid encoding the peptidoglycan hydrolase of the invention, preferably comprising a CHAP domain that has at least one of the most beneficial mutations (i.e. T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1) and / or at least one of the consensus mutation units, as described herein. Preferably, the nucleic acid of the invention is a RNA, preferably a mRNA. Preferably, the RNA, e.g., the mRNA, of the present invention comprises at least one modified nucleoside such as pseudouridine (ψ), N1-methyl-pseudouridine (m1ψ) or 5-methyl-uridine (m5U), preferably N1-methyl- pseudouridine (m1ψ), in place of at least one uridine, preferably in place of multiple, more preferably all uridines. Detailed description of the invention Peptidoglycan hydrolases The term "peptidoglycan hydrolase", as used herein and in context of the present invention, refers to a polypeptide (i.e., a single amino acid chain) which is capable of hydrolyzing peptidoglycan (also called “murein”) of at least one bacterial species or strain, preferably at least one Staphylococcus species or strain, more preferably Staphylococcus aureus. A peptidoglycan hydrolase of the invention may comprise naturally occurring amino acids and / or non- naturally occurring amino acids as well as modifications such as, but not limited to, glycosylation (in particular O- glycosylation and / or N-glycosylation), acetylation, phosphorylation, amidation, palmitoylation, myristoylation, isoprenylation, lipidation, alkylation, or a protective group. Preferably, the peptidoglycan hydrolase of the invention is comprised of at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% or 100% naturally occurring amino acids (which may comprise modifications or not), as described herein. The term "peptidoglycan hydrolase" encompasses, for example, endolysins, lysozymes, tail-spike depolymerases, Virion- associated peptidoglycan hydrolases (VAPGH), bacteriocins and autolysins. In preferred embodiments, the term “peptidoglycan hydrolase” refers to an endolysin. The terms “endolysin” and “lysin” are used interchangeably herein and in context of the present invention. Isolated peptidoglycan hydrolases The peptidoglycan hydrolase of the present invention may be an isolated peptidoglycan hydrolase, e.g., an isolated endolysin. In particular, herein, "isolated" means removed (e.g., purified) from the natural state. For example, a nucleic acid, peptide or polypeptide naturally present in a living animal is not "isolated", but the same nucleic acid, peptide or polypeptide partially or completely separated from the coexisting materials of its natural state is "isolated". An isolated nucleic acid, peptide or polypeptide can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell. Preferably, an isolated peptidoglycan hydrolase, as used herein, refers to a peptidoglycan hydrolase which is isolated (e.g. purified) from its natural context, e.g., from a bacterial cell where it occurs in nature. Engineered and natural peptidoglycan hydrolases In context of the present invention, a “peptidoglycan hydrolase” or an “endolysin”, is, preferably, a modified, i.e., an engineered, “peptidoglycan hydrolase” or “endolysin”, respectively. In particular, a “modified” (i.e., an “engineered”, synthetic”, “recombinant”, or “artificial”) peptidoglycan hydrolase or endolysin does not occur in nature and thus may be also considered herein and in context of the present invention as a “non-natural” (i.e., “non-native”) peptidoglycan hydrolase or endolysin, respectively. Thus, in certain embodiments, the peptidoglycan hydrolase of the invention is an engineered peptidoglycan hydrolase. Furthermore, in certain embodiments, the peptidoglycan hydrolase of the invention is a non-natural peptidoglycan hydrolase. However, in certain embodiments of the invention, the peptidoglycan hydrolases may also include natural (i.e. native) peptidoglycan hydrolases, in particular, natural endolysins, for example, in context of pharmaceutical compositions, medical uses, fusion proteins of a peptidoglycan hydrolase and another (poly)peptide (e.g. a PK tag), RNA constructs, and / or modified nucleic acids, e.g. RNAs containing a modified nucleoside such as N1-methyl- pseudouridine (m1ψ) in place of at least one uridine, as described herein. Endolysins Herein, and in context of the present invention, the term “endolysin” refers, in particular, to natural peptidoglycan hydrolases encoded by bacteriophages (or bacterial viruses), or engineered peptidoglycan hydrolases, in particular modified endolysins, derived from such natural peptidoglycan hydrolases (e.g., from L0482; SEQ ID NO: 1). Natural endolysins act, in particular, by hydrolyzing the host cell wall and subsequently allow the release of bacteriophage progenies. The peptidoglycan hydrolases, e.g., the endolysins, of the present invention are also capable of hydrolyzing peptidoglycan in the cell wall of a bacterial species or strain (e.g., S. aureus) and, thus, have a killing activity against said bacterial species or strain (e.g., S. aureus), as described herein. The term “cell wall” as used herein refers to all components that form the outer cell enclosure of bacteria (containing, in particular, peptidoglycan), as commonly understood in the art. Natural endolysins usually have a molecular weight ranging from about 15 to about 60 kDa, which is also a preferred range for the peptidoglycan hydrolases (e.g. modified endolysins) of the present invention. However, the peptidoglycan hydrolases of the invention may also have a different, e.g., higher, molecular weight, for example when they further comprise additional domains or tags such as a PK tag, as described herein. Moreover, natural endolysins typically have a modular configuration. Herein and in context of the present invention, an endolysin refers, in particular, to a modular endolysin, i.e., a polypeptide (i.e., a single amino acid chain) comprising one or more enzymatically active domains (EADs) and, preferably, additionally one or more cell wall-binding domains (CBDs). Moreover, it is possible, also in context of a modular endolysin, that the endolysin only comprises one module, namely an EAD, e.g. a CHAP domain of the invention, but not a separate cell wall-binding domain. Nevertheless, it is preferred that the peptidoglycan hydrolase of the invention comprises at least one EAD, in particular the CHAP domain of the invention, and additionally at least one CBD. Furthermore, the various domains in a modular endolysin, e.g., an EAD and a CBD, may be separated by linker regions, in particular, by short and flexible linkers, as described herein. An EAD may be N-terminally or C-terminally of a CBD. In L0482 (SEQ ID NO: 1), a single cell wall-binding domain (CBD), i.e. the LYSM domain, is N-terminally of a single enzymatically active domain (EAD), i.e. the CHAP domain. Furthermore, in L0482, the LYSM and CHAP domains are separated by a linker region. L0482 Herein, and in context of the present invention, L0482 (i.e., wild-type L0482; also called “lytN”) has the following sequence, wherein the LYSM domain (positions 1 to 51) is underlined, the linker (positions 52 to 71) is in italics, and the CHAP domain (positions 72 to 215) is in bold: REAPKTQIYTVKKGDTLSAIALKYKTTVSNIQNTNNIANPNLIFIGQKLKVPMTPLVEPKPKTVSSNNKSNSNSSTLNYLKTLEN RGWDFDGSYGWQCFDLVNVYWNHLYGHGLKGYGAKDIPYANNFNSEAKIYHNTPTFKAEPGDLVVFSGRFGG GYGHTAIVLNGDYDGKLMKFQSLDQNWNNGGWRKAEVAHKVVHNYENDMIFIRPFKKA (SEQ ID NO: 1) In the above sequence, the two glycosylation positions in SEQ ID NO: 1, i.e., positions 68 and 73, which may be deleted or, preferably, substituted with another amino acid (e.g., lysine and glycine, respectively) in order to obtain “aglycosylated” L0482 variants (e.g., L0482ag; SEQ ID NO: 2), as described herein, are further highlighted in grey. Furthermore, the positions which may be substituted with the most beneficial amino acid residues contained in the best performing characterized variant, i.e., H5 (SEQ ID NO: 11), as described herein, i.e., positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1, are shown in white on black background. The CHAP domain of L0482 (SEQ ID NO: 1) is further shown in SEQ ID NO: 301; the LYSM domain of of L0482 (SEQ ID NO: 1) is further shown in SEQ ID NO: 302; and the linker region of L0482 (SEQ ID NO: 1) is further shown in SEQ ID NO: 303. In context of the present invention, a natural peptidoglycan hydrolase, in particular the endolysin L0482 (SEQ ID NO: 1), is usually modified by at least one amino acid substitution, as described herein. Furthermore, one or more deletions, insertions and / or additions of amino acid residues may also occur. A modified L0482 protein is also considered herein as an L0482 variant. Furthermore, the peptidoglycan hydrolase according to the present invention, in particular a modified L0482 variant, may lack the LYSM domain or the CHAP domain of L0482, as well as the linker region, as described herein. Alternatively, the LYSM domain or the CHAP domain, as well as the linker region, may be replaced by another cell-wall binding domain or enzymatically active domain, or linker region, respectively, as described herein. Accordingly, the peptidoglycan hydrolase according to the present invention comprises (I) a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1, as described herein; and / or (II) a LYSM domain that has (i) a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO: 1 and (ii) one or more amino acid substitutions as compared to the sequence from position 1 to position 51 in SEQ ID NO: 1, as described herein. Domains of peptidoglycan hydrolases, in particular, of modular endolysins As already indicated above, the enzymatically active domains (EAD) of modular endolysins function, in particular, to cleave certain peptidoglycan bonds in the murein (i.e. peptidoglycan) layer of a host bacterium. Cell wall-binding domains (CBD) are typically enzymatically inactive, and, in particular, recognize and bind to certain epitopes in the cell wall of the host bacterium for proper fixation of the catalytic effect of the EAD. Preferably, herein and in context of the present invention, the cell wall binding domain is a peptidoglycan binding domain which binds, in particular, to the peptidoglycan structure of a target bacterium. The different domains of an endolysin can be connected by a peptide linker, also called “domain linker”. Moreover, as described herein, an EAD (e.g. a CHAP domain) may hydrolyse the peptidoglycan of a target bacterium e.g., the host bacterium, by itself, i.e., without the need for interacting with a separate CBD. For example, an EAD such as a CHAP domain may have (in addition to the peptidoglycan hydrolase activity) some intrinsic cell wall-binding activity and, therefore, have bactericidal activity by itself. This has been already demonstrated, e.g., for some peptidoglycan hydrolases such as lysozyme. In particular, binding of a substrate in the cell wall of a target bacterium to or close to the catalytic pocket of an EAD may be sufficient to initiate docking and subsequent lysis of the bacterium. Therefore, a CHAP domain of the invention may be also considered herein and in context of the present invention as a peptidoglycan hydrolase which may have a bactericidal activity by itself. Accordingly, a peptidoglycan hydrolase according to the present invention comprises at least one enzymatically active domain (EAD) which is also called “catalytic domain” herein. Preferably, said at least one enzymatically active domain comprises at least a CHAP domain of the invention, as described herein, i.e., a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1. Enzymatic peptidoglycan cleavage mechanisms As used herein, the term “peptidoglycan hydrolase” is, in general, not restricted to a specific enzymatic cleavage mechanism. In particular, an enzymatically active domain of a peptidoglycan hydrolase may function as a glycosidase, as an amidase (i.e. an amidohydrolase) and / or as a peptidase. Hence, a peptidoglycan hydrolase comprising one or more EADs as described herein and in context of the present invention, e.g., an endolysin, may function as a glycosidase, an amidase and / or a peptidase. As used herein, glycosidases such as acetylmuramidases, lytic transglycosylases or glucosaminidases generally cleave the backbone of glycan. In particular glycosidases may cleave the β-1,4 glycosidic bonds linking alternating polymeric structures of N-acetylmuramic acids (MurNAc) and N-acetylglucosamines (GlcNAc) in a peptidoglycan layer. Amidases (i.e. amidohydrolases) generally cleave the side- chain peptide, in particular they may catalyze the cleavage of amide bonds between the MurNAc and the first amino acid in the peptide stem moiety, i.e., L-alanine. Peptidases (in particular, endopeptidases and carboxypeptidases) generally cleave within the peptide side-chain, in particular they may cleave bonds between two amino acids of the stem peptide of peptidoglycan, whereby bond cleavage can either occur within interpeptide bridge or stem peptide– interpeptide bridge. Herein and in context of the present invention, the term “CHAP domain” refers to a cysteine, histidine-dependent amidohydrolase / peptidase domain which is an enzymatically active domain (EAD) of a peptidoglycan hydrolase (in particular of a L0482 variant), as described herein. A CHAP domain may be further considered herein and in context of the present invention as a peptidoglycan hydrolase. Moreover, the CHAP domain of L0482 (SEQ ID NO: 1) may function as an amidase and as a peptidase in order to hydrolyse peptidoglycan. In particular, it has been reported that the CHAP domain has an N-acetylmuramyl L-Ala amidase activity and a D-Ala-Gly endopeptidase activity; Frankel (2012), J Biol Chem.23;287(13). Hence, the CHAP domain of the invention may also function, in particular, as an amidase and / or as a peptidase, preferably as an amidase and as a peptidase. Accordingly, the peptidoglycan hydrolase of the present invention functions, preferably, as an amidase (i.e. it has, preferably, an amidase activity) and / or as a peptidase (i.e. it has, preferably, a peptidase activity). In particular, the peptidoglycan hydrolase of the present invention may have an N- acetylmuramyl L-Ala amidase activity and / or a D-Ala-Gly endopeptidase activity. More preferably the peptidoglycan hydrolase of the present invention functions as an amidase and as a peptidase, in particular, wherein it may have an N-acetylmuramyl L-Ala amidase activity and a D-Ala-Gly endopeptidase activity. Moreover, a CHAP domain which functions as an amidase and / or as a peptidase in order to hydrolyse peptidoglycan, may be also considered herein and in context of the present invention as a peptidoglycan hydrolase with amidase and / or peptidase activity, respectively. Thus, the CHAP domain of the invention may be a peptidoglycan hydrolase with amidase (e.g. N-acetylmuramyl L-Ala amidase activity) and / or peptidase activity (e.g. D-Ala-Gly endopeptidase activity). Accordingly, a peptidoglycan hydrolase of the present invention comprising the CHAP domain of the invention has, preferably, an amidase and / or peptidase activity, as described herein. Herein, and in context of the present invention, hydrolyzing peptidoglycan in the cell wall of a bacterium may refer also to breaking down and / or cleaving said peptidoglycan. Bactericidal activity Hydrolyzing, in particular breaking down and / or cleaving, peptidoglycan in the cell wall of a bacterium, usually kills the bacterium. Therefore, the peptidoglycan hydrolase of the present invention has, in particular, a bactericidal activity. Herein, and in context of the present invention, the term “bactericidal activity” refers to the ability of a peptidoglycan hydrolase to kill at least one bacterium, i.e., at least one bacterial species or strain, in particular at least one target bacterium (i.e., a bacterial species or strain to be killed). Preferably, a peptidoglycan hydrolase of the invention has the ability to kill at least one gram-positive bacterium, more preferably a Staphylococcus species or strain, most preferably at least Staphylococcus aureus, preferably, including methicillin-resistant Staphylococcus aureus (MRSA) strains. A peptidoglycan hydrolase which has the ability to kill a certain bacterium, e.g., S. aureus, is also referred to herein as a peptidoglycan hydrolase which has a “killing activity” against said bacterium, e.g., S. aureus. Herein and in context of the present invention, the killing activity of a peptidoglycan hydrolase against a certain bacterium, e.g., S. aureus, is preferably measured by determining the minimum concentration at which the peptidoglycan hydrolase growth-inhibits a liquid culture of said bacterium, e.g., S. aureus. Said minimum concentration is also referred to herein as “minimal inhibitory concentration” (MIC). Herein and in context of the present invention, the “minimal inhibitory concentration” (MIC) is, in particular, defined as the minimum concentration which keeps the optical density at 620 nm (OD620) of a liquid culture comprising 5x105cfu / ml of a target bacterium (e.g., S. aureus) below 0.1 for at least 24h at 37°C incubation. Preferably, the culture medium of said liquid culture is cation adjusted Müller-Hinton broth (caMHB) medium supplemented with 25% horse serum, in particular, when the target bacterium is a Staphylococcus species or strain such as S. aureus. When the killing activity against S. aureus is measured, the S. aureus cells in the liquid culture correspond, preferably, to 5x105cfu / ml of ATCC43300 which is a methicillin-resistant Staphylococcus aureus (MRSA) strain. The term “cfu” is the abbreviation of “colony forming units”, and refers to the estimated number of viable bacterial cells as commonly understood in the art. A detailed assay for measuring the killing activity against a target bacterium, e.g., a Staphylococcus species or strain such as S. aureus, is provided in Example 6: First, a peptidoglycan hydrolase (e.g., a L0482 variant of the present invention) is produced in E. coli, as described in Example 6 under the heading “Production of L0482 variants in E. coli”. Then, the peptidoglycan hydrolase (e.g., the L0482 variant of the present invention) is purified from E. coli, as described under the heading “Purification of L0482 variants from E. coli” in Example 6. Finally, the bactericidal activity of the peptidoglycan hydrolase (e.g., the L0482 variant of the present invention) against a target bacterium (e.g. S. aureus) is determined as described in Example 6 under the heading “Determination of bactericidal activity of L0482 variants”. Detailed assays for measuring the killing activity of a peptidoglycan hydrolase against a biofilm or free-floating aggregate of a target bacterium, e.g., a biofilm or free-floating aggregate of Staphylococcus species or strain such as S. aureus, are provided in Example 6 under the heading “Determination of anti-biofilm activity of L0482 variants” which may be preferably employed. One of these assays makes use of a peg biofilm in plasma (PBA) and is particularly well suitable for determining the killing activity of a peptidoglycan hydrolase against a classical biofilm that is attached to a surface. The other assay makes use of a free-floating aggregate in synovial fluid (FBA) and is particularly well suitable for determining the killing activity of a peptidoglycan hydrolase against a free-floating (biofilm-like) aggregate. As used herein and in context of the present invention, the term “activity” of a peptidoglycan hydrolase refers, in particular, to the bactericidal activity of the peptidoglycan hydrolase, as described herein. Furthermore, because the bactericidal activity of a peptidoglycan hydrolase against a certain bacterial species or strain, e.g. S. aureus as described herein, is tightly correlated to its capability of hydrolyzing (and breaking down and / or cleaving) peptidoglycan in the cell wall of said bacterial species or strain, it is not necessary to further measure or determine the ability of the peptidoglycan hydrolase according to the present invention to hydrolyze, break down and / or cleave peptidoglycan by an enzymatic assay; it is sufficient to determine the bactericidal activity of the peptidoglycan hydrolase, i.e., its killing activity against the bacterial species or strain, e.g. S. aureus, as described herein. In other words, a peptidoglycan hydrolase (e.g. an endolysin) according to the present invention is considered to implicitly have the ability to hydrolase peptidoglycan in a target bacterium when it is able to kill said target bacterium, as described herein. However, to further corroborate that a peptidoglycan hydrolase functions indeed as a “peptidoglycan hydrolase”, it is also possible to perform additional assays. For example, the reduction of purified peptidoglycan at OD620 nm in the present of a peptidoglycan hydrolase of the invention may be easily measured. Furthermore, purified peptidoglycan may be incubated with a peptidoglycan hydrolase of the invention followed by analysis and identification of cleavage products by mass spectrometry. Furthermore, the YODA-derived method of screening yeast cells for the secretion of an active peptidoglycan hydrolase according to the invention, as described herein may be employed. As described herein, in said screening method, the “activity” of a peptidoglycan hydrolase, i.e., its killing activity against a certain bacterium, is determined by measuring its ability to break down peptidoglycan contained in dead bacterial cells of said bacterium and / or fragments thereof or corresponding peptidoglycan particles (in particular via hydrolysis of the peptidoglycan). Gram-positive and gram-negative bacteria In gram-positive bacteria, the cytoplasmic membrane is surrounded by a peptidoglycan layer. A main purpose of the cell wall of Gram-positive bacteria is to maintain the shape of the bacteria and counteract the pressure inside the bacterial cells. Peptidoglycan or murein is a polymer composed of sugar and amino acid. The sugar component is composed of N-acetylglucosamine residues and a N-acetylmuramic acid residues that are β-(1,4) linked. A peptide chain consisting of 3 to 5 amino acids is bound to N-acetylmuramic acid. Peptide chains can be cross-linked to peptide chains of other chains to form a 3D mesh-like layer. The peptide chain can contain D- and L-amino acid residues, and its composition can vary depending on the type of bacteria. In contrast to gram-positive bacteria, gram-negative bacteria have an outer membrane with a characteristic asymmetric bilayer. The outer membrane bilayer consists of an inner monolayer containing phospholipids (primarily phosphatidylethanolamine) and an outer monolayer composed primarily of lipopolysaccharide (LPS). This outer membrane overlays a peptidoglycan layer which is normally much thinner than in gram-positive bacteria. As described herein, the peptidoglycan hydrolase of the invention has, in particular, a killing activity against at least one gram-positive bacterium, preferably a Staphylococcus species or strain, more preferably at least Staphylococcus aureus, as described herein. Variants and sequence identity to a reference sequence Herein and in context of the present invention, a polypeptide (e.g., a peptidoglycan hydrolase of the invention) or a part thereof (e.g., a CHAP domain of the invention) which is derived from a certain polypeptide (e.g. L0482) or a part thereof (e.g. the CHAP domain of L0482) is considered herein and in context of the present invention as a “variant” of said polypeptide or part thereof, respectively, (e.g. a L0482 variant or CHAP domain variant, respectively). Furthermore, a peptidoglycan hydrolase of the invention comprising a CHAP domain of the invention, i.e., a CHAP domain derived from the CHAP domain of L0482, is also considered herein and in context of the present invention as an L0482 variant. Herein, and in context of the present invention, the terms “variant” and “mutant” may be used interchangeably. A variant (e.g. the CHAP domain of the invention) has, in particular, a sequence identity of at least n % (i.e. at least 60%) to a corresponding reference sequence (e.g. the sequence from position 72 to position 215 in SEQ ID NO: 1). Herein, a reference sequence, usually, refers to the sequence of the (poly)peptide or part thereof from which the variant is derived (e.g. the CHAP domain of L0482). Moreover, it is possible that a variant itself is employed as a reference sequence (e.g. H5; SEQ ID NO: 11) for describing another variant. Furthermore, a variant, i.e. a polypeptide (e.g., a peptidoglycan hydrolase of the invention) or a part thereof (e.g., a CHAP domain of the invention) which is derived from a certain polypeptide (e.g. L0482) or a part thereof (e.g. the CHAP domain of L0482) that is used as a reference sequence, has at least one mutation, i.e., at least one amino acid substitution, deletion, insertion and / or addition, preferably at least one amino acid substitution, relative to the reference sequence (e.g. at least one mutation in SEQ ID NO: 1, or in the sequence from position 72 to position 215 in SEQ ID NO: 1, respectively). As commonly understood in the art and as also used herein and in context of the present invention, the term “sequence identity”, refers to the extent to which two (nucleotide or amino acid) sequences have the same residues at the same positions in an alignment. Typically, the “sequence identity” is expressed as a percentage. Moreover, one of the two sequences may be considered as a reference sequence to which the other sequence has a sequence identity of at least n %. Thus, herein and in context of the present invention, a certain (poly)peptide (e.g., a peptidoglycan hydrolase of the invention) or a part thereof (e.g., a CHAP domain of the invention) can be structurally defined by having a sequence identity of at least n % to a corresponding reference sequence, with n being an integer between 60 and 99, in particular 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99. As just mentioned above, said reference sequence refers to a (poly)peptide (e.g. SEQ ID NO: 1) or a part thereof (e.g. the sequence from position 72 to position 215 in SEQ ID NO: 1) from which said (poly)peptide or part thereof is derived, respectively. Furthermore, it may be specifically indicated herein and in context of the present invention that a certain polypeptide or part thereof has a higher minimal sequence identity to a corresponding reference sequence than “at least 60%”, i.e., a sequence identity of at least n %, with n being an integer between 61 and 99. For example, when the sequence identity is at least 80%, n is an integer between 80 and 99. Furthermore, when it is indicated herein that a certain polypeptide or part thereof has a minimal sequence identity of at least 90% to a corresponding reference sequence, i.e., a sequence identity of at least n %, with n being an integer between 90 and 99, n may also refer to a decimal number with one decimal place between 89.5 and 99.9, in particular, 89.5, 89.6, 89.7, 89.9, 90.0, 90.1, 90.2 etc. or 99.9. In particular, when the minimal sequence identity is indicated by an integer, i.e., at least n % with n being an integer (e.g. at least 95%), n may also refer to a decimal number with one decimal place that can be rounded by conventional rounding rules to said integer. For example, a sequence identity of at least 95% may also refer to a sequence identity of at least 94.5%, at least 94.6%, at least 94.7%, at least 94.8%, at least 94.9%, at least 95.0%, at least 95.1%, at least 95.2%, at least 95.3% or at least 95.4%. Generally, herein and in context of the present invention, the higher the sequence identity to a reference sequence, the more preferred it is. Furthermore, certain minimal sequence identities (other than “at least 60%”) are indicated herein in specific contexts and thus are considered as preferred minimal sequence identities in these contexts. However, other minimal sequence identities to a reference sequence, in particular, a sequence identity of at least n %, with n being an integer between 60 and 99, or n % with n being a decimal number with one decimal place between 89.5 and 99.9, are considered herein as well in context of any (poly)peptide or part thereof described herein. Of note, the term “(poly)peptide”, as used herein, can refer to a polypeptide or a peptide, as commonly understood in the art. The degree of sequence identity can be determined according to methods well known in the art using, preferably, suitable computer algorithms such as BLAST and / or CLUSTAL Omega. In particular, BLAST may be used in combination with CLUSTAL Omega. Furthermore, such computer algorithms such as BLAST allow to identify and compare peptidoglycan hydrolase variants having at certain sequence coverage (e.g. at least 80%) and a sequence identity (e.g. at least 60%) to a reference sequence. The coverage is a filter that selects sequences with the same architecture as the reference sequence, e.g., LYSM-CHAP endolysins. For example, in context of the present invention and as illustrated in the appended Examples, endolysin sequences were isolated from the NCBI nucleotide database using BLAST, wherein the sequences were first sorted with a cutoff of 80% sequence coverage and then with a cutoff of 60% identity to L0482 (SEQ ID NO: 1) or a certain variant thereof. CLUSTAL Omega was then employed to align the sequences. When using the Clustal Omega analysis method (e.g. in combination with BLAST) to determine whether a particular sequence is, for instance, at least 60% identical to a reference sequence default settings may be used. Preferably, Clustal Omega (Madeira F, Park YM, Lee J, et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Research. 2019 Jul;47(W1):W636-W641. DOI: 10.1093 / nar / gkz268. PMID: 30976793; PMCID: PMC6602479) is used for the comparison of amino acid sequences in context of the present invention. In the case of pairwise comparisons / alignments, the following default settings are preferably chosen: Program : clustalo; Version : 1.2.4; Input Parameters: Output guide tree: true; Output distance matrix: false; Dealign input sequences: false; mBed-like clustering guide tree: true; mBed-like clustering iteration: true; Number of iterations: 0; Maximum guide tree iterations: -1; Maximum HMM iterations: -1; Output alignment format: clustal_num; Output order: aligned; Sequence Type: protein. Preferably, the degree of sequence identity is calculated over the complete length of the reference sequence. Amino acid residues located at a position corresponding to a position in a reference sequence, e.g., the amino acid sequence shown in SEQ ID NO:1, can be easily identified by the skilled person by methods known in the art. For example, such amino acid residues can be identified by aligning the sequence in question with the reference sequence, e.g., the sequence shown in SEQ ID NO:1, and by identifying the positions which correspond to the indicated positions in the reference sequence, e.g. in SEQ ID NO:1. The alignment can be done with means and methods known to the skilled person, e.g. by using a known computer algorithm such as the Lipman-Pearson method (Science 227 (1985), 1435) or the CLUSTAL algorithm. It is preferred that in such an alignment maximum homology is assigned to conserved amino acid residues present in the amino acid sequences. Preferably, Clustal Omega is used for the comparison of amino acid sequences in context of the present invention, and hence for determining positions corresponding to positions in a reference sequence. In the case of pairwise comparisons / alignments, the following default settings are preferably chosen: Program : clustalo; Version : 1.2.4; Input Parameters: Output guide tree: true; Output distance matrix: false; Dealign input sequences: false; mBed- like clustering guide tree: true; mBed-like clustering iteration: true; Number of iterations: 0; Maximum guide tree iterations: -1; Maximum HMM iterations: -1; Output alignment format: clustal_num; Output order: aligned; Sequence Type: protein. When the amino acid sequences (e.g. of L0482 variants) are aligned by means of such a method, regardless of insertions, deletions or additions that occur in the amino acid sequences, the positions of the corresponding amino acid residues can be determined (e.g., in each of the L0482 variants). For example, SEQ ID NO: 1 (WT L0482) has a length of 215 amino acids and an arginine (“R”) at position 86. The L0482 hit variant H3 (SEQ ID NO: 9), for example, does not show any deletions, insertions or additions compared to the sequence of SEQ ID NO: 1 but has a lysine (“K”) at position 86. Thus, H3 (SEQ ID NO: 9) has an amino acid substitution at position 86 in reference to SEQ ID NO: 1, wherein the residue at said position (i.e., the arginine) is substituted with lysine. In short, H3 has the R86K mutation in reference to SEQ ID NO: 1, as described herein. In the L0482 hit variant “H1” (SEQ ID NO: 7), however, five amino acid residues are deleted at the N-terminus. Thus, H1 only has a length of 210 amino acid residues. However, by aligning SEQ ID NO: 1 and SEQ ID NO: 7 by standard means as described herein and as illustrated in the appended Examples, it is immediately evident that H1 (SEQ ID NO: 7) has a lysine (“K”) at a position corresponding to position 86 in SEQ ID NO: 1, similarly as H3; see, e.g., Figure 9A. Thus, H1 (SEQ ID NO: 7) is considered herein and in context to the present invention to have an amino acid substitution at a position corresponding to position 86 in SEQ ID NO: 1, wherein the residue at said position (i.e., the arginine) is substituted with lysine. In short, H1 has the same R86K mutation in reference to SEQ ID NO: 1 as other hit variants such as H3. A similar logic also applies to any other mutations, e.g., amino acid substitutions, described herein and in context of the present invention. Herein and in the context of the present invention, an “amino acid substitution” or short “substitution” at a certain position in a reference amino acid sequence or at a position corresponding to a certain position in a reference sequence (e.g. in SEQ ID NO: 1) means that the amino acid residue at said position is substituted with another amino acid residue, as described herein. In particular, the terms “amino acid substitution” or “substituted with another amino acid residue” mean that the respective amino acid residue at the indicated position can be substituted with any other possible amino acid residue, e.g. a naturally occurring amino acid or a non-naturally occurring amino acid (Brustad and Arnold, Curr. Opin. Chem. Biol.15 (2011), 201-210), preferably with a naturally occurring amino acid, i.e., an amino acid residue selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine. Herein and in the context of the present invention, in particular with respect to mutations within amino acid sequences, “deleted” or “deletion” means that the amino acid at the indicated position is deleted. Herein and in the context of the present invention, in particular with respect to mutations within amino acid sequences, “inserted” or “insertion” means that at the respective position at least one amino acid residue, e.g., one or two, preferably one residue, is inserted after the indicated position. Herein and in the context of the present invention, in particular with respect to mutations within amino acid sequences, “added” or “addition” means that at least one amino acid residue is added at the N-terminus and / or the C-terminus of the reference sequence. Furthermore, a standard tool, preferably Clustal Omega, is used for determining the sequence identity of a nucleic acid sequence to a corresponding reference nucleic acid sequence in context of the present invention, preferably by using default settings. CHAP domain of the invention and peptidoglycan hydrolases comprising a CHAP domain of the invention As described herein above, the present invention relates, in some aspects, to a peptidoglycan hydrolase comprising a CHAP domain according to the present invention. In particular, said peptidoglycan hydrolase has bactericidal activity, preferably a killing activity against a gram-positive bacterium, more preferably against Staphylococcus species or strain, most preferably against Staphylococcus aureus, preferably including methicillin-resistant Staphylococcus aureus strains, as described herein. The peptidoglycan hydrolase of the invention may have a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, as described herein. In particular, herein and in context of the present invention, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1, and has (ii) one or more amino acid substitutions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1, as described herein. Furthermore, the CHAP domain of the invention may have one or more amino acid deletions, insertions or additions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1. However, the extent of the amino acid substitutions, deletions, insertions and / or additions may not be such that the sequence identity of the CHAP domain of the invention to the sequence from position 72 to position 215 in SEQ ID NO: 1 is below 60%. In particular, the CHAP domain according to the invention functions as a peptidoglycan hydrolase and, preferably, has bactericidal activity, as described herein. As already mentioned above, the sequence from position 72 to position 215 in SEQ ID NO: 1 is also shown in SEQ ID NO: 301. Thus, the CHAP domain according to the invention has, in other words, a sequence identity of at least 60% to the sequence of SEQ ID NO: 301 and one or more amino acid substitutions as compared to the sequence of SEQ ID NO: 301. As described herein, the comparison to a reference sequence comprises, in particular, performing a sequence alignment. Thus, regardless of the occurrence of any amino acid deletions, insertions or additions, positions in the CHAP domain of the invention corresponding to positions in SEQ ID NO: 1 can be readily identified. In particular, in the absence of any deletions, insertions or additions, the CHAP domain of the invention has one or more amino acid substitutions in the sequence from position 72 to position 215 in SEQ ID NO: 1. Otherwise, the CHAP domain of the invention may have one or more amino acid substitutions in the sequence from a position corresponding to position 72 in SEQ ID NO: 1 to a position corresponding to position 215 in SEQ ID NO: 1, i.e., in the sequence which corresponds to the sequence from position 72 to position 215 in SEQ ID NO: 1 in a sequence alignment (and which may have deletions, insertions and / or additions relative to the sequence from position 72 to position 215 in SEQ ID NO: 1). In this context, it is not necessary that positions corresponding to positions 72 and 215 are present in the CHAP domain of the invention because other positions between these positions are sufficient to perform a sequence alignment. In certain embodiments, the peptidoglycan hydrolase of the invention consists of the CHAP domain of the invention, in particular, a sequence that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1. In particular, said CHAP domain (and hence said peptidoglycan hydrolase) has bactericidal activity, preferably a killing activity against a Staphylococcus species or strain, more preferably against Staphylococcus aureus, as described herein. Thus, in some aspects, the invention relates to the CHAP domain of the invention, i.e. a CHAP domain which has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1, and which has (ii) one or more amino acid substitutions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1, as described herein. In particular, the CHAP domain of the invention may be advantageously employed in a peptidoglycan hydrolase of the invention (e.g. in combination with a cell wall binding domain) or considered itself as a peptidoglycan hydrolase of the invention. In certain embodiments, the peptidoglycan hydrolase of the invention (i.e., a peptidoglycan hydrolase comprising or consisting of the CHAP domain of the invention), has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1. This sequence identity is, in particular, calculated over the full length of the sequence of SEQ ID NO: 1 (and not over the full length of the sequence of the peptidoglycan hydrolase of the invention). Thus, any additional domains, peptides or tags that may be comprised in (or fused to) the peptidoglycan hydrolase of the invention, e.g., a signal peptide or a PK tag, should not be considered when determining the sequence identity of the peptidoglycan hydrolase of the invention to the sequence of SEQ ID NO: 1. Hence, the peptidoglycan hydrolase of the invention may comprise (I) an amino acid sequence having a sequence identity of at least 60% to the sequence of SEQ ID NO: 1 (comprising the CHAP domain of the invention, and optionally the LYSM domain and / or peptide linker of the invention), and, optionally, (II) one or more further domains, peptides or tags, e.g. a signal peptide, a PK tag, a further peptide linker etc., as described herein. In particular, said CHAP domain has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1, and has (ii) one or more amino acid substitutions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1, as described herein. Aglycosylation mutations As described herein and as illustrated in the appended Examples, the removal of glycosylation sites in L0482 (i.e. at positions 68 and 73 in SEQ ID NO: 1) resulting in so-called “aglycosylated” L0482 variants strongly enhanced the bactericidal activity upon expression in eukaryotic cells; see, e.g., Example 4. Position 68 in SEQ ID NO: 1 is in the linker sequence of L0482, whereas position 73 in SEQ ID NO: 1 is in the CHAP domain of L0482. As already mentioned above, the CHAP domain is considered herein and in context of the invention as particularly important for the function of the peptidoglycan hydrolases of the invention, especially more important than the linker. Thus, an aglycosylation mutation at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is more preferred in context of the present invention than an aglycosylation mutation at position 68 in SEQ ID NO: 1 or at a position corresponding to this position. Thus, in some embodiments, e.g., in context of aglycosylation mutations and aglycosylated L0482 variants, the inventive CHAP domain of the invention has a mutation, in particular, an amino acid substitution or a deletion, at position 73 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, e.g., as specified in the subsequent embodiments. In other words, in the CHAP domain of the invention, the arginine (“N”) at position 73 in SEQ ID NO: 1 or the arginine at a position corresponding to position 73 in SEQ ID NO: 1 may be deleted or, preferably, substituted with another amino acid residue, as described herein. As further described herein, said position 73 may be considered herein and in context of the present invention as a glycosylation position which is, preferably, aglycosylated. Therefore, the inventive CHAP domain of the invention has preferably an aglycosylation mutation, preferably an amino acid substitution, at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Thus, in some preferred embodiments, the inventive CHAP domain of the invention has an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, in particular, an aglycosylation substitution as described herein. In certain embodiments, e.g., in context of a mutation or substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, the peptidoglycan hydrolase of the invention does not have a sequence as shown in any one of SEQ ID NO: 276 to 278. Herein and in context of the present invention, in particular in context of the inventive CHAP domain, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position may be, for example, substituted with another amino acid residue than methionine, phenylalanine or lysine. In certain embodiments, e.g., with respect to peptidoglycan hydrolases consisting of the inventive CHAP domain and / or lacking a cell wall binding domain as described herein, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with another amino acid residue than methionine. In further embodiments of the inventive peptidoglycan hydrolase or CHAP domain, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with another amino acid residue than phenylalanine or lysine. Preferably herein and in context of the present invention, in particular in context of the inventive CHAP domain and / or aglycosylation substitutions, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, for example, glycine, tyrosine, leucine, glutamic acid, alanine, or histidine. In some embodiments, in particular in context of the inventive peptidoglycan hydrolase and / or the inventive CHAP domain, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with another amino acid residue than phenylalanine, lysine or serine. Preferably herein and in context of the present invention, in particular in context of the inventive CHAP domain and / or aglycosylation substitutions, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. For example, the CHAP domain of the invention may have a sequence as shown in positions 72 to 215 in SEQ ID NO: 2. In certain embodiments, in particular in context of a peptidoglycan hydrolase that has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, the peptidoglycan hydrolase of the invention further comprises a deletion or an amino acid substitution (preferably an amino acid substitution) at position 68 in SEQ ID NO: 1 or at a position corresponding to this position. In other words, the arginine at position 68 in SEQ ID NO: 1 or at a position corresponding to this position may be deleted or, preferably, substituted with another amino acid residue, as described herein. As already indicated above, a mutation at position 68 in SEQ ID NO: 1 or at a position corresponding to this position may be considered herein and in context of the present invention as an aglycosylation mutation, in particular in context of a peptidoglycan hydrolase having a sequence identity of at least 60% to the sequence of SEQ ID NO: 1. In certain embodiments, in particular in context of the inventive peptidoglycan hydrolase that has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted, for example, with another amino acid residue than threonine, serine or lysine, e.g., another amino acid residue than threonine or serine. In certain embodiments, in particular in context of the inventive peptidoglycan hydrolase that has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with another amino acid residue than threonine, serine or lysine, e.g. another amino acid residue than threonine or serine, and / or the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with another amino acid residue than phenylalanine, lysine or serine, e.g., another amino acid residue than phenylalanine or lysine. In certain preferred embodiments, in particular in context of the inventive peptidoglycan hydrolase that has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, methionine, arginine or alanine, preferably lysine. In addition, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position may be substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably glycine. In certain preferred embodiments, in particular in context of the inventive peptidoglycan hydrolase that has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, the peptidoglycan hydrolase has a pair of amino acid substitutions at positions 68 and 73 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein a) the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, and the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, serine, tyrosine or leucine, b) the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with methionine, and the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, c) the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, and the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, or d) the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, and the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or histidine. In certain particularly preferred embodiments, in particular in context of the inventive peptidoglycan hydrolase that has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, the residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, and the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. As already mentioned above, a peptidoglycan hydrolase of the invention having at least one aglycosylation mutation, in particular in the CHAP domain, (e.g. an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position such as K73G, for example as show in SEQ ID NO: 2) is, inter alia, a particularly good starting point for further protein engineering and / or directed evolution. Thus, the peptidoglycan hydrolase of the invention may have instead or in addition (preferably in addition) to the mutations at positions 68 and / or 73 in SEQ ID NO: 1 or at positions corresponding to these positions, as described herein, for example in the embodiments just above, at least one amino acid substitution described herein in context of beneficial / permissive, particularly beneficial or most beneficial amino acid substitutions found in L0482 variants obtained by the directed evolution (see, e.g., Examples 5-7) or found in context of deimmunization analyses or experiments (see, e.g., Example 10). Beneficial / permissive, particularly beneficial, most beneficial amino acid or deimmunizing amino acid substitutions are described herein, for example, in the following. Beneficial and permissive amino acid substitutions found by the aglycosylation screen, directed evolution or the in silico deimmunization screen As described herein and as illustrated in the appended Examples, the inventors found 252 L0482 variants that were active and secreted from eukaryotic cells. These variants contained various amino acid substitutions which are considered herein as beneficial or at least permissive with respect to the pharmaceutical properties of the peptidoglycan hydrolases of the invention; see, e.g., Example 7 and Table 3. In particular, said amino acid substitutions may be beneficial (or at least permissive) for the bactericidal activity (e.g. against S. aureus) and the ability of being secreted from eukaryotic cells (e.g. human cells) of L0482 variants, as described herein. Furthermore, the deimmunizing amino acid substitutions identified in silico may be considered as beneficial for the safety and / or efficacy of the L0482 variants in context of medical uses and at least permissive for other pharmaceutical properties such as the bactericidal activity; see, e.g., Example 10 and Table 5. Furthermore, the inventors found amino acid substitutions at position 73 in SEQ ID NO: 1, i.e. aglycosylation substitutions in the CHAP domain of L0482, which enhance the bactericidal activity upon expression in eukaryotic cells; see, e.g., Example 4. The term “at least permissive” means that introducing a corresponding amino acid substitution does not abrogate the functionality of an L0482 variant as a pharmaceutical. In other words, a permissive amino acid substitution, as used herein, does not worsen the pharmaceutical properties of an L0482 variant to extent that it no longer can be used as a pharmaceutical. As a minimal requirement for being useful as a pharmaceutical, a L0482 variant must have a bactericidal activity as described herein. Furthermore, the L0482 variant should, ideally, have a sufficient stability as described herein when being used as a pharmaceutical. When the L0482 variant is provided in form of a nucleic acid (e.g. an RNA) for medical uses, the L0482 variant should, ideally, further have the ability of being secreted from a mammalian cell. However, it is not necessary that a permissive amino acid substitution renders a L0482 variant suitable for a pharmaceutical use by itself or improves the pharmaceutical properties of a L0482 variant. Thus, permissive amino acid substitutions may be rather employed in combination with at least one particularly beneficial amino acid substitution, or, preferably, with at least one of the most beneficial amino acid substitutions, as described herein. A “beneficial” amino acid substitution, as used herein, may improve or contribute to the improvement of at least one pharmaceutical property of a L0482 variant, e.g., the bactericidal activity, the ability of being secreted from mammalian cells, the stability and / or the reduction of the immunogenicity. Although beneficial amino acid substitution may be employed alone, they are, preferably, employed in combination with at least one particularly beneficial amino acid substitution, or, more preferably, with at least one of the most beneficial amino acid substitutions, as described herein. Thus, in some embodiments, in particular in context of permissive / beneficial and / or deimmunizing mutations, as well as active and secreted L0482 variants obtained by directed evolution, the CHAP domain of the invention has one or more amino acid substitutions at positions 72 to 83, 85, 86, 93, 96, 99, 102 to 104, 107, 108, 111, 113 to 115, 117, 121 to 125, 129 to 131, 133 to 145, 148, 149, 152, 153, 155, 157, 159, 166, 169, 170, 173 to 178, 185, 186, 190 to 194, 196 to 199, 201, 203 to 207, and 212 to 215 in SEQ ID NO: 1, or at positions corresponding to these positions. Preferably, in these embodiments, the amino acid residue at position 72 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, aspartic acid, histidine or threonine, the amino acid residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine, serine, aspartic acid or threonine, the amino acid residue at position 74 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine or proline, the amino acid residue at position 75 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, proline, aspartic acid or glutamine, the amino acid residue at position 76 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, aspartic acid or asparagine, the amino acid residue at position 77 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, aspartic acid, glycine, histidine, lysin, asparagine, glutamine, serine, or threonine, the amino acid residue at position 78 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or tyrosine, the amino acid residue at position 79 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine or tryptophan, the amino acid residue at position 80 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, aspartic acid, methionine or asparagine, the amino acid residue at position 81 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, arginine, serine, alanine or glycine, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or glycine, the amino acid residue at position 83 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, methionine or tyrosine, the amino acid residue at position 93 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or leucine, the amino acid residue at position 96 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 99 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, methionine, glutamine, threonine or valine, the amino acid residue at position 102 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, glycine, serine or threonine, the amino acid residue at position 103 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or glycine, the amino acid residue at position 104 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, aspartic acid, methionine, glutamine or tyrosine, the amino acid residue at position 107 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, tyrosine or alanine, the amino acid residue at position 108 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, glycine, lysine or tyrosine, the amino acid residue at position 111 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 113 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 114 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or threonine, the amino acid residue at position 115 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, aspartic acid, glycine or serine, the amino acid residue at position 117 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, aspartic acid or asparagine, the amino acid residue at position 121 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 122 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 123 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, serine, threonine or tryptophan, the amino acid residue at position 124 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, histidine, glutamine or threonine, the amino acid residue at position 125 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 129 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or serine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, isoleucine, asparagine or tyrosine, the amino acid residue at position 131 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, glutamine or tyrosine, the amino acid residue at position 133 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, threonine or glutamine, the amino acid residue at position 134 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, valine, lysine or glutamine, the amino acid residue at position 135 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine, histidine or serine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, arginine, glutamic acid or threonine, the amino acid residue at position 137 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 138 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 139 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, aspartic acid, glutamine or serine, the amino acid residue at position 140 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or aspartic acid, the amino acid residue at position 141 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, aspartic acid, histidine or threonine, the amino acid residue at position 142 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or arginine, the amino acid residue at position 143 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with proline, the amino acid residue at position 144 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid or glutamine, the amino acid residue at position 145 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or leucine, the amino acid residue at position 148 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine or valine, the amino acid residue at position 149 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or threonine, the amino acid residue at position 152 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 153 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine or serine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 157 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 159 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 166 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, glutamic acid or threonine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine or aspartic acid, the amino acid residue at position 170 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, histidine or serine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, asparagine or arginine, the amino acid residue at position 174 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, histidine, lysine, arginine, serine or threonine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, glutamine or threonine, the amino acid residue at position 176 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, arginine, alanine, glutamine, serine or threonine, the amino acid residue at position 177 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 178 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, arginine, serine or threonine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, histidine, serine, tyrosine or aspartic acid or asparagine, the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 190 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, alanine, cysteine, aspartic acid, histidine, asparagine, serine or threonine, the amino acid residue at position 191 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, arginine, aspartic acid or asparagine, the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, threonine, glutamic acid, glycine or lysine, the amino acid residue at position 193 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 194 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, glycine, proline or threonine, the amino acid residue at position 196 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or threonine, the amino acid residue at position 197 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or proline, the amino acid residue at position 198 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 199 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, asparagine, serine or threonine, the amino acid residue at position 201 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, serine or lysine, the amino acid residue at position 203 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid or valine, the amino acid residue at position 204 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, serine or tyrosine, the amino acid residue at position 205 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or valine, the amino acid residue at position 206 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 207 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, valine, histidine or tryptophan, the amino acid residue at position 212 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, aspartic acid, glutamic acid, histidine, lysin or asparagine, the amino acid residue at position 213 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, tyrosine or threonine. the amino acid residue at position 214 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or threonine, and / or the amino acid residue at position 215 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, valine or serine. The amino acid substitutions just listed herein above correspond to the amino acid residues shown in Example 7 in Table 3 in the column “beneficial / permissive residues” which are not surrounded by parentheses, i.e. not marked by “( )”, as well as the amino acid residues shown in Example 10 in Table 5 in the column “deimm”. In particular, the positions (short: “pos”) in Tables 3 and 5 corresponds to the positions in SEQ ID NO: 1. Thus, an amino acid residue listed at a certain position in these Tables means that the amino acid at said position or at a position corresponding to said position in SEQ ID NO: 1 is substituted with an amino acid residue indicated at said position in the column “beneficial / permissive residues” in Table 3 and / or in the column “deimm” in Table 5. As an illustrative example in this context, “ER(H)” in the column “beneficial / permissive residues” in Table 3 means that the amino acid residue (i.e. the lysine; “K”) at position 176 in SEQ ID NO: 1 or at a position corresponding to position 176 SEQ ID NO: 1 is substituted with glutamic acid (“E”) or arginine (“R”) in the L0482ag variants that were secreted from yeast cells and found to be active by YODA, as described herein and as illustrated in the appended Examples. Thus, said mutations, i.e. amino acid substitutions, are considered herein and in context of the present invention as “beneficial” or at least “permissive” for the desired pharmaceutical properties of peptidoglycan hydrolases, in particular, a sufficient killing activity (e.g., against S. aureus), a sufficient stability and a sufficient ability of being secreted from eukaryotic cells. Furthermore, the amino acid residues shown within parentheses in the column “beneficial / permissive residues” in Table 3 (e.g. the histidine “(H)” at position 176 in the above illustrative example) may be also at least permissive for said pharmaceutical properties. Table 3 shows positions in SEQ ID NO: 1 where beneficial or permissive amino acid substitutions have been found. These are the positions for which the column “beneficial / permissive residues” in Table 3 shows at least one amino acid residue, regardless of whether said residue is shown without parentheses or in parentheses. These positions are also called “permissive positions” herein. Furthermore, positions 72 to 215 in Table 3 for which the column “beneficial / permissive residues” shows at least one amino acid residue, regardless of whether said residue is shown without parentheses or in parentheses are considered as “permissive positions” in the CHAP domain herein. Herein and in context of the present invention, an amino acid residue in SEQ ID NO: 1 corresponding to a beneficial or permissive position may be substituted with an amino acid residue shown in the column “beneficial / permissive residues” in Table 3 for said position, i.e. a residue shown without parentheses or in parentheses in said column in Table 3, preferably with a residue that is shown without parentheses in said column in Table 3. In some embodiments, in particular in context of permissive / beneficial mutations and Table 3, the CHAP domain of the present invention has at least one amino acid substitution at the permissive positions in the CHAP domain or at positions corresponding to said permissive positions in the CHAP domain. Preferably, in these embodiments, at least one amino acid residue at said permissive positions in the CHAP domain or at positions corresponding to said permissive positions in the CHAP domain is substituted with an amino acid residue shown in the column “beneficial / permissive residues” in Table 3 for said positions, more preferably with a residue that is shown without parentheses in said column in Table 3. In some embodiments, in particular in context of a peptidoglycan hydrolase having a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, permissive / beneficial mutations and Table 3, the peptidoglycan hydrolase of the present invention has at least one amino acid substitution at the permissive positions or at positions corresponding to said permissive positions. Preferably, in these embodiments, at least one amino acid residue at said permissive positions or at positions corresponding to said permissive positions is substituted with an amino acid residue shown in the column “beneficial / permissive residues” in Table 3 for said positions, more preferably with a residue that is shown without parentheses in said column in Table 3. Thus, in certain embodiments, in particular in context of permissive / beneficial mutations, as well as active and secreted L0482 variants obtained by directed evolution, the CHAP domain of the invention has one or more amino acid substitutions at positions 72 to 76, 78, 81, 82, 85, 86, 93, 96, 104, 107, 108, 111, 113, 115, 117, 121, 124, 125, 129, 130, 133 to 136, 138, 140 to 142, 144, 145, 148, 149, 152, 153, 155, 157, 159, 169, 173, 175 to 178, 185, 186, 190 to 194, 197, 198, 199, 201, 203, 204, 207, and 212 to 215 in SEQ ID NO: 1, or at positions corresponding to these positions. Preferably, in these embodiments, the amino acid residue at position 72 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine or serine, the amino acid residue at position 74 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine or proline, the amino acid residue at position 75 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine or proline, the amino acid residue at position 76 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 78 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or tyrosine, the amino acid residue at position 81 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, arginine or serine, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or methionine, the amino acid residue at position 93 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or leucine, the amino acid residue at position 96 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 104 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 107 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or tyrosine, the amino acid residue at position 108 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 111 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 113 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 115 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 117 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, the amino acid residue at position 121 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 124 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine or histidine, the amino acid residue at position 125 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 129 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or serine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, isoleucine or asparagine, the amino acid residue at position 133 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or threonine, the amino acid residue at position 134 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine or valine, the amino acid residue at position 135 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine or histidine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, the amino acid residue at position 138 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 140 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or aspartic acid, the amino acid residue at position 141 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 142 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or arginine, the amino acid residue at position 144 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 145 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or leucine, the amino acid residue at position 148 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine or valine, the amino acid residue at position 149 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or threonine, the amino acid residue at position 152 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 153 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine or serine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 157 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 159 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, asparagine or arginine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, glutamine or threonine, the amino acid residue at position 176 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or arginine, the amino acid residue at position 177 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 178 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine or arginine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, histidine, serine or tyrosine, the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 190 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 191 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or arginine, the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or threonine, the amino acid residue at position 193 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 194 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 197 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 198 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 199 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 201 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid or serine, the amino acid residue at position 203 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid or valine, the amino acid residue at position 204 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, serine or tyrosine, the amino acid residue at position 207 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine or valine, the amino acid residue at position 212 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 213 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine or threonine. the amino acid residue at position 214 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine or threonine, and / or the amino acid residue at position 215 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, valine or serine. The amino acid substitutions described just herein above refer to all the substitutions found in the sequenced L0482 variants that were secreted from yeast cells and determined to be active by the YODA method as described herein and as illustrated in the appended Examples; see, e.g., Example 7 and Table 3, in particular the “beneficial / permissive residues” shown without parentheses in Table 3. Particularly beneficial amino acid substitutions Furthermore, the inventors determined hit variants among all these L0482 variants, which are particularly well adapted for the production in eukaryotic cells and which may have particularly beneficial pharmaceutical properties, as described herein; see, e.g., Examples 5-7, Table 4 and Figures 8 and 9. As described herein, the amino acid substitutions found in these hit variants, i.e. G1-G4, H1-H10 and I1-I30, are considered herein and in context of the present invention as “particularly beneficial mutations” or “particularly beneficial amino acid substitutions” which may be particularly beneficial for maintaining or enhancing the desired pharmaceutical properties of peptidoglycan hydrolases, in particular, the bactericidal activity (e.g., against S. aureus), the stability and / or the ability of being secreted from eukaryotic cells, e.g. human cells. Herein, and in context of the present invention, the particularly beneficial amino acid substitutions are preferred over amino acid substitutions that are described as “beneficial” or “permissive” herein. Accordingly, in some preferred embodiments, the CHAP domain of the invention has one or more amino acid substitutions at positions 73, 75, 78, 81, 82, 85, 86, 104, 107, 115, 124, 125, 130, 133, 135, 136, 140, 141, 155, 169, 173, 175, 178, 185, 186, 191, 192, 194, 198, 204, 212 and 215 in SEQ ID NO: 1 or at positions corresponding to these positions. Preferably, in these embodiments, the amino acid residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine or serine, the amino acid residue at position 75 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 78 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 81 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 104 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 107 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 115 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 124 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 125 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 133 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 135 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, the amino acid residue at position 140 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 141 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 178 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 191 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 194 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 198 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 204 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 212 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue at position 215 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine. In further preferred embodiments, the CHAP domain of the invention has an aglycosylation mutation at position 73 or at a position corresponding to this positions, as described herein, and additionally one or more amino acid substitutions at positions 75, 78, 81, 82, 85, 86, 104, 107, 115, 124, 125, 130, 133, 135, 136, 140, 141, 155, 169, 173, 175, 178, 185, 186, 191 to 194, 198, 204, 212 and 215 in SEQ ID NO: 1 or at positions corresponding to these positions, as described herein, for example, as just described herein above. G1 as an exemplary first-round hit variant comprising particularly beneficial amino acid substitutions G1 (SEQ ID NO: 3) is a hit variant obtained in the first round of the directed evolution, which showed an increased thermostability, an enhanced bactericidal activity and an enhanced secretion from eukaryotic cells as compared to the starting for the directed evolution (L0482ag); see Figure 8. G1 (SEQ ID NO: 3) contains the following amino acid substitutions in the CHAP domain as compared to L0482ag (SEQ ID NO: 2): T82S, N85G, R86K, D169N, K173N, M175Q and A192Q. Thus, in some embodiments, the CHAP domain of the invention has one or more amino acid substitutions at positions 82, 85, 86, 169, 173, 175 and 192 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position (i.e. threonine) is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position (i.e. asparagine) is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position (i.e. arginine) is substituted with lysine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position (i.e. aspartic acid) is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position (i.e. lysin) is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position (i.e. methionine) is substituted with glutamine, and / or the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position (i.e. alanine) is substituted with glutamine. Furthermore, the CHAP domain may have a sequence identity of at least 95% to the sequence from position 72 to position 215 in SEQ ID NO: 3. In some embodiments, the CHAP domain has (a) an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; (b) an amino acid substitution pair at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, and the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; and / or (c) an amino acid substitution at position 169 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine. Furthermore, said CHAP domain may comprise one or more amino acid substitutions at positions 173, 175 and 192 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, and / or the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine. Preferably, the CHAP domain further has an aglycosylation mutation at position 73 or at a position corresponding to this position, as described herein, preferably wherein the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, more preferably with glycine. In some embodiments of the present invention, the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 80% to the sequence from position 72 to position 215 in SEQ ID NO: 1; (ii) an amino acid substitution or a deletion at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and (iii) one or more amino acid substitutions at positions 82, 85, 86, 169, 173, 175 and 192 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, and / or the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine; with the proviso that said CHAP domain does not have a sequence as set forth in SEQ ID NO: 381, 382, 383, 384 or 385. In some embodiments of the present invention, the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 91% to the sequence from position 72 to position 215 in SEQ ID NO: 1; (ii) an amino acid substitution or a deletion at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and (iii) one or more amino acid substitutions at positions 82, 85, 86, 169, 173, 175 and 192 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, and / or the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine; with the proviso that said CHAP domain does not have a sequence as set forth in SEQ ID NO: 381 or 382. In some further embodiments of the invention, the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 80% to the sequence from position 72 to position 215 in SEQ ID NO: 1; (ii) an amino acid substitution or a deletion at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and (iii) at least two amino acid substitutions at positions 82, 85, 86, 169, 173, 175 and 192 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, and / or the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine. In some embodiments of the invention, the peptidoglycan hydrolase comprises a CHAP domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; (ii) an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; and (iii) one or more amino acid substitutions at positions 82, 85, 86, 169, 173, 175 and 192 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, and / or the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine. Most beneficial amino acid substitutions As described herein and as illustrated in the appended Examples, the inventors found a set of most beneficial mutations, in particular a set of 9 most beneficial amino acid substitutions, i.e., T82S, N85G, R86K, S130N, H136K / R (preferably H136K), F155Y, D169N, N185Y and N186G in reference to SEQ ID NO: 1. As described herein, the variant H5 (SEQ ID NO: 11) which has been found to have overall the best pharmaceutical properties among the L0482 variants obtained by two rounds of directed evolution, contains exclusively these 9 most beneficial amino acid substitutions; see, e.g., Figures 8 and 9. In particular, H5 (SEQ ID NO: 11) has a strongly enhanced ability of being secreted from human cells, a strongly enhanced killing activity against S. aureus, and an improved (thermo)stability as compared to the parental L0482ag (SEQ ID NO: 2) and also as compared to WT L0482 (SEQ ID NO: 1); see, e.g., Examples 4-6 and 12 and Figures 8, 10 and 6. In particular, H5 (SEQ ID NO: 11) showed a 8-fold lower MIC than WT L0482 (SEQ ID NO: 1), i.e. WT L0482 had a MIC of 4 µg / ml, whereas H5 had a MIC of 0.5 µg / ml. Moreover, H5 (SEQ ID NO: 11) showed the strongest killing activity against S. aureus (together with H7; SEQ ID NO: 13), the best stability (in particular a melting temperature of 47°C), and a good secretion from human cells; see Figure 8. H5 also showed an enhanced ability of being secreted from human cells, an enhanced killing activity against S. aureus, and an improved (thermo)stability as compared to G1 (SEQ ID NO: 3) which is an improved L0482 variant obtained in the first round of the directed evolution; see Figure 8. In particular, G1 had a MIC of 1 µg / ml, whereas H5 had a MIC of 0.5 µg / ml. H5 (SEQ ID NO: 11) further showed enhanced (i.e. faster) killing kinetics against S. aureus in an OD reduction assay than WT L0482 (SEQ ID NO: 1); see Example 6 and Figure 11. In addition, H5 (SEQ ID NO: 11) effectively killed S. aureus biofilms and showed an even greater anti-biofilm activity than G1 (SEQ ID NO: 3); see Example 6 and Figure 12. This is in line with the particularly low MIC observed for H5, which is lower than the MIC of G1. Thus, the most beneficial amino acid substitutions (i.e the “H5” mutations) are particularly beneficial for enhancing the desired pharmaceutical properties of peptidoglycan hydrolases, in particular, the bactericidal activity (e.g., against S. aureus including S. aureus biofilms), the stability and / or the ability of being secreted from eukaryotic cells, e.g. human cells. In context of the present invention, the most beneficial amino acid substitutions are preferred over amino acid substitutions described as “particularly beneficial” and even more preferred over amino acid substitutions described as “beneficial” or “permissive”. As already mentioned above, it has been further found in context of the present invention that the L0482 variant H3 (SEQ ID NO: 9) obtained by the directed evolution contained 8 out of the 9 most beneficial amino acid substitutions and exclusively these 8 mutations. Since the 8 “H3” amino acid substitutions occurred recurrently in slightly different combinations among the 44 hit variants obtained by three rounds of directed evolution, they are considered herein and in context of the present invention as the consensus mutations. Furthermore, H3 reflects the consensus sequence. In particular, the 8 consensus mutations refer to T82S, N85G, R86K, S130N, H136K / R, D169N, N185Y and N186G, in reference to the sequence of SEQ ID NO: 1. Furthermore, as described herein and as illustrated in the appended Examples, H3 (SEQ ID NO: 9) has improved pharmaceutical properties, e.g., an improved ability of being secreted from eukaryotic cells compared to WT L0482 and L0482ag as well as a good killing activity against S. aureus; see, e.g., Figures 8 and 10. This further demonstrates the advantageous effects of the consensus mutations with respect to the pharmaceutical properties of L0482 variants, as described herein. Thus, in some particularly preferred embodiments, e.g., in context of the consensus mutations, the CHAP domain of the present invention has one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions. Preferably, in these embodiments, the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In other words, the CHAP domain of the invention has, in some particularly preferred embodiments, at least one consensus mutation, i.e. at least one amino acid substitution selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, D169N, N185Y and N186G in SEQ ID NO: 1. Preferably, said CHAP domain (i.e. a CHAP domain comprising at least one of the consensus mutations described herein) further comprises (i) an aglycosylation mutation at position 73 or at a position corresponding to this position, as described herein, for example, wherein the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably glycine or serine, more preferably glycine; and / or (ii) an amino acid substitution at position 155 or at a position corresponding to this position, wherein the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine. As also already mentioned above, it has been surprisingly found in context of the invention that the L0482 variant H5 (SEQ ID NO: 11) which had an enhanced killing activity against S. aureus, an enhanced stability (e.g thermostability / melting temperature) and an enhanced ability of being secreted from human cells (Figure 8) as compared to H3, differed from H3 by only one amino acid, i.e., it had, in addition to the consensus mutations, the amino acid substitution F155Y in reference to SEQ ID NO: 1 (Figure 9). Furthermore, it has been found that the amino acid substitution H136R occurred in many of the hit variants (i.e. G1-G4, H1-H10 and I1 to I30) instead of H136K and thus is a very good alternative to H136K. In particular, the L0482 variant H3 has the following sequence, wherein the LYSM domain (positions 1 to 51) is underlined, the linker (positions 52 to 71) is in italics, and the CHAP domain (positions 72 to 215) is in bold: REAPKTQIYTVKKGDTLSAIALKYKTTVSNIQNTNNIANPNLIFIGQKLKVPMTPLVEPKPKTVSSNKKSNSGSSTLNYLKSLEG KGWDFDGSYGWQCFDLVNVYWNHLYGHGLKGYGAKDIPYANNFNNEAKIYKNTPTFKAEPGDLVVFSGRFGG GYGHTAIVLNGNYDGKLMKFQSLDQNWYGGGWRKAEVAHKVVHNYENDMIFIRPFKKA (SEQ ID NO: 9). Furthermore, the L0482 variant H5 has the following sequence, wherein the LYSM domain (positions 1 to 51) is underlined, the linker (positions 52 to 71) is in italics, and the CHAP domain (positions 72 to 215) is in bold: GYGHTAIVLNGNYDGKLMKFQSLDQNWYGGGWRKAEVAHKVVHNYENDMIFIRPFKKA (SEQ ID NO: 11). In the above H3 and H5 sequences (i.e SEQ ID NO: 9 and SEQ ID NO 11, respectively), the two glycosylation positions, i.e., positions 68 and 73, wherein aglycosylation amino acid residues have been introduced in H3 and H5 (i.e. lysine at position 68 and glycine at position 73) are highlighted in grey. The amino acid residues in SEQ ID NO: 9 shown in white on black background refer to the consensus mutations, and the amino acid residues in SEQ ID NO: 11 shown in white on black background refer to the most beneficial amino acid substitutions, as described herein and in context of the present invention. Of note, H3 (SEQ ID NO: 9) contains all of the most beneficial amino acid substitutions except F155Y. Also see Figure 9A for the alignments. Notably, all of the most beneficial amino acid substitutions, i.e. T82S, N85G, R86K, S130N, H136K / R (preferably H136K), F155Y, D169N, N185Y and N186G in reference to SEQ ID NO: 1, occurred within the CHAP domain of L0482, i.e. within the sequence from position 72 to position 215 in SEQ ID NO: 1. Herein and in context of the present invention any of these most beneficial mutations or any combination thereof is, preferably, combined with an aglycosylation mutation at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein, e.g., with the amino acid substitution N73G in SEQ ID NO: 1. In certain embodiments, e.g. in context of a peptidoglycan hydrolase which has a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, any of these most beneficial mutations or any combination thereof is further combined with at least one aglycosylation mutation at positions 68 and 73 in SEQ ID NO: 1 or at positions corresponding to these positions, as described herein, e.g., with the amino acid substitutions N68K and / or N73G in SEQ ID NO: 1. However, it is by no means necessary that the peptidoglycan hydrolase or CHAP domain of the invention contains all of the 9 most beneficial mutations described herein at once. For example, it has been found that the L0482 variant H1 (SEQ ID NO: 7) did not show any mutations at positions corresponding to positions 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 and, nevertheless, had enhanced pharmaceutical properties compared to the parental L0482ag lysin (SEQ ID NO: 2), in particular, an enhanced killing activity against S. aureus, an enhanced stability (e.g. thermostability / melting temperature), and an enhanced ability of being secreted from human cells. As a further example, it has been found that the L0482 variant H9 (SEQ ID NO: 15) did not show any mutations at positions corresponding to positions 82, 85, 155, 185 and 185 in SEQ ID NO: 1, and also showed enhanced pharmaceutical properties compared to the parental L0482ag lysin (SEQ ID NO: 2); see, e.g., Figures 8 and 9. In fact, the amino acid substitution R86K is the only one among the most beneficial substitutions which H1 (SEQ ID NO: 7) and H9 (SEQ ID NO: 15) have in common. This clearly demonstrates that the most beneficial amino acid substitutions found in context of the present invention may be employed in various combinations and reliably enhance the pharmaceutical properties of L0482-derived peptidoglycan hydrolases, as described herein. However, this finding does, in no way, contradict the notion that the group of the most beneficial amino acid substitutions described herein has been purposefully and carefully selected by the present inventors in order to improve the pharmaceutical properties of L0482-derived peptidoglycan hydrolases. For example, when the additional amino acid substitutions N185Y and N186G are introduced in H9 (SEQ ID NO: 15) resulting, e.g., in G4 (SEQ ID NO: 6), H2 (SEQ ID NO: 8), H8 (SEQ ID NO: 14) or H10 (SEQ ID NO: 16), some or all of the pharmaceutical properties assayed can be further improved; see Figure 8 and 9. Furthermore, as already mentioned above, the single amino acid substitution F155Y (occurring, e.g., in H5) improved all pharmaceutical properties compared to H3, further demonstrating that individual most beneficial amino acid substitutions can already have highly beneficial effects. In fact, the L0482 variant H5 (SEQ ID NO 11) which had all of the most beneficial mutations described herein and exclusively these mutations, showed the best pharmaceutical properties among all hit variants analyzed, as described herein. Thus, in some particularly preferred embodiments, e.g., in context of the most beneficial amino acid substitutions, the CHAP domain of the present invention has one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions. Preferably, in these embodiments, the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In other words, the CHAP domain of the invention has, in some particularly preferred embodiments, at least one amino acid substitution selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1. Preferably, said CHAP domain (i.e. a CHAP domain comprising at least one of the most beneficial amino acid substitutions described herein) further comprises an aglycosylation mutation at position 73 or at a position corresponding to this position, as described herein, for example, wherein the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably glycine or serine, more preferably glycine. Amino acid substitution pairs and consensus mutation units As further described herein above, the inventors further surprisingly found that certain amino acid substitutions, in particular some of the consensus mutations (i.e. T82S, N85G, R86K, S130N, H136K / R (esp. H136K), D169N, N185Y and N186G in reference to SEQ ID NO: 1) occurred very often as substitution pairs in the active and secreted L0482 variants obtained by the directed evolution, in particular in the hits variants, i.e., G1 to G4, H1 to H10 and I1 to I30. Thus, the consensus mutations (which are particularly preferred amino acid substitutions in context of the invention) may be further grouped as consensus mutation units herein and in context of the present invention. As mentioned above, these consensus mutation units consist of 1 or 2 amino acid substitutions and refer to: (i) R86K (which is particularly preferred), (ii) T82S and N85G, (iii) S130N and H136K / R (preferably H136K), (iv) D169N, and (v) N185Y and N186G. Thus, in some preferred embodiments, e.g., in context of the most beneficial amino acid substitutions and / or consensus mutation units, the CHAP domain of the invention has at least one pair of amino acid substitutions a) at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, b) at positions 130 and 136 in SEQ ID NO: 1 or at positions corresponding to these positions, and / or c) at positions 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions. In context of these embodiments, in a), preferably, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, and the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; in b), preferably, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, and the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine; and / or in c), preferably, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In other words, the CHAP domain of the invention has, in some preferred embodiments, at least one substitution pair selected from the group consisting of: a) T82S and N85G, b) S130N and H136K / R (preferably H136K), and c) N185Y and N186G. Furthermore, said CHAP domain (i.e. a CHAP domain having at least one substitution pair) further has, preferably, an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Furthermore, said CHAP domain (i.e. a CHAP domain having at least one substitution pair, and preferably an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position) further has, preferably, an amino acid substitution at position 155 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Furthermore, said CHAP domain, has, preferably, an aglycosylation mutation at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. In some further preferred embodiments, the CHAP domain of the present invention has at least one consensus mutation unit, i.e., at least one amino acid substitution or substitution pair selected from the group consisting of the following (i) to (v): (i) an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at said position is substituted with lysine (i.e. R86K); (ii) an amino acid substitution at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine (i.e. T82S), and the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine (i.e. N85G); (iii) an amino acid substitution at positions 130 and 136 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine (i.e. S130N), and the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine (i.e. H136K / R), preferably lysine (H136K); (iv) an amino acid substitution at position 169 (i.e. the aspartic acid) in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at said position is substituted with asparagine (i.e. D169N); and (v) an amino acid substitution at positions 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine (i.e. N185Y), and the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine (i.e. N186G). Preferably, in context of these embodiments, the CHAP domain of the invention has at least 2, preferably at least 3, more preferably at least 4 of the amino acid substitutions or substitution pairs (i) to (v) (i.e. consensus mutation units), as just described herein above. In some particularly preferred embodiments, the CHAP domain of the invention has (i) an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at said position is substituted with lysine; and has at least one, preferably at least two, more preferably at least three of the following amino acid substitutions or substitution pairs (ii) to (v) (i.e. consensus mutation units): (ii) an amino acid substitution at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, and the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; (iii) an amino acid substitution at positions 130 and 136 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, and the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine; (iv) an amino acid substitution at position 169 (i.e. the aspartic acid) in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at said position is substituted with asparagine; and / or (v) an amino acid substitution at positions 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. Generally, herein and in context of the present invention, a consensus mutation or any combination thereof (i.e. at least one substitution selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, D169N, N185Y and N186G, in SEQ ID NO: 1) or a consensus mutation unit or any combination thereof (i.e. at least one consensus mutation unit selected from the group consisting of: (i) R86K, (ii) T82S and N85G, (iii) S130N and H136K / R, (iv) D169N, (v) N185Y and N186G) is, preferably, combined with an amino acid substitution at position 155 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Preferably, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine (i.e. F155Y), as described herein. Furthermore, generally herein and in context of the present invention, a consensus mutation or consensus mutation unit or any combination thereof (which may be further combined with F155Y as just described) is, preferably, combined with at least one aglycosylation mutation (preferably at least one aglycosylation substitution) as described herein, preferably an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position. Preferably, the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, more preferably, with glycine, as described herein. What has been just described herein above in context of an amino acid substitution at position 155 in SEQ ID NO: 1 or at a position corresponding to this position, an aglycosylation mutation, and an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is, in particular, also the case for the following embodiments: In some preferred embodiments, the CHAP domain of the invention has the amino acid substitution R86K, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S and N85G, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, S130N and H136K / R, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K and D169N, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K and N185Y and N186, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, S130N and H136K / R, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, and D169N, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, and N185Y and N186G, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, D169N, N185Y and N186G, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, S130N, H136K / R, N185Y and N186G, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, S130N, H136K / R, and D169N, as described herein. In some preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, N185Y and N186G, as described herein. In some particularly preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, S130N, H136K / R and D169N, as described herein. In some particularly preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, S130N, H136K / R, N185Y and N186, as described herein. In some particularly preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, S130N, H136K / R, D169N, N185Y and N186G, as described herein. In some particularly preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, D169N, N185Y and N186G, as described herein. In some of the most preferred embodiments, the CHAP domain of the invention has the amino acid substitutions R86K, T82S, N85G, S130N, H136K / R, D169N, N185Y and N186G, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions T82S and N85G, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions T82S, N85G, S130N and H136K / R, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions T82S, N85G and D169N, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions T82S, N85G, N185Y and N186G, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions T82S, N85G, S130N, H136K / R and D169N, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions T82S, N85G, S130N, H136K / R, N185Y and N186G, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions T82S, N85G, S130N, H136K / R, D169N, N185Y and N186G, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions S130N and H136K / R, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions S130N, H136K / R and D169N, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions S130N, H136K / R, N185Y and N186G, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions S130N, H136K / R, D169N, N185Y and N186G, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitution D169N, as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions D169N, N185Y and N186G as described herein. In some embodiments, the CHAP domain of the invention has the amino acid substitutions N185Y and N186G, as described herein. Furthermore, herein and context of the present invention, and hence, also in the above embodiments, the substitution H136K is preferred over the substitution H136R. Particularly important individual amino acid substitutions: R86K and F155Y As already mentioned above and as illustrated in the appended Examples, all hit variants, i.e. G1-G4, H1-H10 and I1-I30, had the amino acid substitution R86K in reference to SEQ ID NO: 1. Thus, this amino acid substitution is considered herein and in context of the present invention as a particularly important substitution among the most beneficial amino acid substitutions, as described herein. Thus, in some of the most preferred embodiments, e.g., in context of the most beneficial amino acid substitutions, the CHAP domain of the present invention has an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position. For example, in context of these embodiments, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position may be substituted with another amino acid residue than serine. Preferably, in context of these embodiments, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or methionine. More preferably, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine. Furthermore, said CHAP domain, has, preferably, an aglycosylation mutation at position 73 in SEQ ID NO 1 or at a position corresponding to this position, as described herein. As also already mentioned above, the amino acid substitution F155Y further improved several pharmaceutical properties (e.g. the killing activity against S. aureus, the stability and the ability of being secreted from human cells) in H5 (SEQ ID NO: 11) compared to H3 (SEQ ID NO: 9) containing only the consensus mutations. Therefore, in some preferred embodiments, the CHAP domain of the invention has an amino acid substitution at position 155 in SEQ ID NO: 1 or at a position corresponding to this position. Preferably, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine. Generally, herein and in context of the present invention, the CHAP domain, has, preferably, an aglycosylation mutation at position 73 in SEQ ID NO 1 or at a position corresponding to this position, as described herein. This is also true, inter alia, for all the following embodiments: Further embodiments In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 91% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; and has (iii) one or more amino acid substitutions at positions 82, 85, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the peptidoglycan hydrolase of the invention has (i) a sequence identity of at least 84% to the sequence of SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; and has (iii) one or more amino acid substitutions at positions 82, 85, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 78% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; and has (iii) at least two amino acid substitutions at positions 82, 85, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the peptidoglycan hydrolase of the invention has (i) a sequence identity of at least 73% to the sequence in SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; and has (iii) at least two amino acid substitutions at positions 82, 85, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 78% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; and has (iii) one or more amino acid substitutions at positions 82, 85, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the peptidoglycan hydrolase of the invention has (i) a sequence identity of at least 73% to the sequence in SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; and has (iii) one or more amino acid substitutions at positions 82, 85, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; and has (iii) at least six amino acid substitutions at positions 82, 85, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; has (iii) an amino acid substitution at position 82 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine; and has (iv) an amino acid substitution at position 85 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In other words, said CHAP domain has the R86K substitution and a substitution pair consisting of T82S and N85G in reference to SEQ ID NO: 1. In some particular embodiments, the peptidoglycan hydrolase of the invention has (i) a sequence identity of at least 60% to the sequence of SEQ ID NO: 1; has (ii) an amino acid substitution at position 86 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; has (iii) an amino acid substitution at position 82 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine; and has (iv) an amino acid substitution at position 85 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In other words, said peptidoglycan hydrolase has the R86K substitution and the substitution pair consisting of T82S and N85G in reference to SEQ ID NO: 1. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 83% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution or a deletion (preferably, an amino acid substitution) at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and has (iii) one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the peptidoglycan hydrolase of the invention has (i) a sequence identity of at least 73% to the sequence of SEQ ID NO: 1; has (ii) an amino acid substitution or a deletion (preferably, an amino acid substitution) at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and has (iii) one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; and (ii) an amino acid substitution at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue (i.e. the asparagine) at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. Preferably, said CHAP domain further has (iii) one or more amino acid substitutions at positions 82, 85, 86, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution or a deletion (preferably, an amino acid substitution) at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and has (iii) an amino acid substitution at position 82 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution or a deletion (preferably, an amino acid substitution) at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and has (iii) an amino acid substitution at position 130 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 73 or a deletion (preferably, an amino acid substitution) in SEQ ID NO: 1 or at a position corresponding to this position; and has (iii) an amino acid substitution at position 185 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 130 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine; and has (iii) one or more amino acid substitutions at positions 82, 85, 86, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 78% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 155 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine; and has (iii) at least two amino acid substitutions at positions 82, 85, 86, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the peptidoglycan hydrolase of the invention has (i) a sequence identity of at least 73% to the sequence of SEQ ID NO: 1; has (ii) an amino acid substitution at position 155 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine; and has (iii) at least two amino acid substitutions at positions 82, 85, 86, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 78% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 155 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine; and has (iii) one or more amino acid substitutions at positions 82, 85, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some embodiments, the peptidoglycan hydrolase of the invention has (i) a sequence identity of at least 73% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 155 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine; and has (iii) one or more amino acid substitutions at positions 82, 85, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some particular embodiments, the CHAP domain of the invention has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; has (ii) an amino acid substitution at position 155 in SEQ ID NO: 1, or at a position corresponding to this position, wherein the amino acid residue (i.e. the phenylalanine) at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine; and has (iii) at least six amino acid substitutions at positions 82, 85, 86, 130, 136, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue (i.e. the threonine) at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue (i.e. the asparagine) at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue (i.e. the arginine) at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue (i.e. the serine) at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the histidine) at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably lysine, the amino acid residue (i.e. the aspartic acid) at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue (i.e. the asparagine) at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue (i.e. the asparagine) at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine. In some embodiments, e.g., in context of L0482 variants obtained by the directed evolution, permissive or beneficial mutations, particularly beneficial mutations, most beneficial mutations, consensus mutations or consensus mutation units, the peptidoglycan hydrolase of the invention does not have a sequence as shown in any one of SEQ ID NO: 279 to 293. In some embodiments, the CHAP domain of the present invention has a sequence identity of at least 90%, preferably at least 95%, more preferably at least 97% or at least 98%, e.g. at least 97.3%, to the CHAP domain of a hit variant as described herein, i.e., to the CHAP domain of any one of G1 to G4, H1 to H10 and I1 to I30 (SEQ ID NO: 3 to 46, respectively), as described herein. In particular, the CHAP domain of a hit variant (e.g. H1) refers to the sequence from a position in the sequence of said hit variant (e.g. SEQ ID NO: 7) which corresponds to position 72 in SEQ ID NO: 1 to a position in the sequence of said hit variant (e.g. SEQ ID NO: 7) which corresponds to position 215 in SEQ ID NO: 1. In particular, said CHAP domain has at least one of the amino acid substitutions selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1, i.e. with respect to the sequence from position 72 to position 215 in SEQ ID NO: 1 as a reference sequence, as described herein. In some further embodiments, the peptidoglycan hydrolase of the present invention has a sequence identity of at least 90%, preferably at least 95%, more preferably at least 97%, e.g. at least 96.8%, to a hit variant as described herein, i.e., to any one of SEQ ID NO: 3 to 46. In particular, said peptidoglycan hydrolase has at least one of the amino acid substitutions selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1, i.e. with respect to SEQ ID NO: 1 as a reference sequence, as described herein. In some preferred embodiments, the CHAP domain of the invention has a sequence identity of at least 93.2% or at least 94% to the sequence from position 72 to position 215 in SEQ ID NO: 11. In particular, said CHAP domain has at least one of the amino acid substitutions selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1, i.e. with respect to the sequence from position 72 to position 215 in SEQ ID NO: 1 as a reference sequence, as described herein. In some preferred embodiments, the peptidoglycan hydrolase of the invention has a sequence identity of at least 95.0% or at least 96% to the sequence of SEQ ID NO: 11. In particular, said peptidoglycan hydrolase has at least one of the amino acid substitutions selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1, i.e. with respect to SEQ ID NO: 1 as a reference sequence, as described herein. In some preferred embodiments, the CHAP domain of the invention has a sequence identity of at least 93.9% or at least 94% to the sequence from position 72 to position 215 in SEQ ID NO: 9. In particular, said CHAP domain has at least one of the amino acid substitutions selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1, i.e. with respect to the sequence from position 72 to position 215 in SEQ ID NO: 1 as a reference sequence, as described herein. In some preferred embodiments, the peptidoglycan hydrolase of the invention has a sequence identity of at least 95.4% or at least 96% to the sequence of SEQ ID NO: 9. In particular, said peptidoglycan hydrolase has at least one of the amino acid substitutions selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1, i.e. with respect to SEQ ID NO: 1 as a reference sequence, as described herein. Conserved positions and conserved segment In some embodiments, a segment of the inventive CHAP domain has a sequency identity of at least 80%, preferably at least 90%, to the sequence from position 87 to position 128 in SEQ ID NO: 1. In particular, said segment is contained in the inventive CHAP domain at positions corresponding to positions 87 to 128 in SEQ ID NO: 1, i.e., it is a corresponding segment. As shown, e.g., in Example 7, said segment may be considered herein and in context of the present invention as a particularly conserved CHAP segment. Furthermore, in some of these embodiments or in other embodiments, the CHAP domain of the invention has at most six, five, four, three or two, more preferably at most one, most preferably no amino acid substitutions or deletions at positions 80, 87, 88, 98, 99, 103, 106, 110, 114, 122, 126, 128, 137, 182, 202, and 208 of SEQ ID NO: 1 or at positions corresponding to these positions. As shown, e.g., in Example 7, said positions may be considered herein and in context of the present invention as conserved positions within the CHAP domain. In context of the present invention, the CHAP domain of the invention has, preferably, one or more amino acid substitutions at other positions than at the conserved positions described herein. Nevertheless, the CHAP domain may also comprise one or more mutations, e.g. amino acid substitutions, at the conserved positions. For example, the in-silico de-immunizing screen illustrated in Example 10 revealed possible amino acid substitutions at many different positions including “conserved positions”. Of note, this de-immunizing screen has been designed such that advantageous pharmaceutical properties, in particular the bactericidal activity, stability and ability of being secreted from eukaryotic cells, are maintained upon the de-immunization. Thus, mutations such as the de-immunization mutations found in context of the invention may be also introduced at positions which are considered as “conserved” herein. Moreover, a conserved CHAP segment has in context of the present invention, preferably, less mutations than other segments of the CHAP domain of the invention. Thus, a corresponding segment of the CHAP domain of the invention has, preferably, a higher sequency identity (e.g. about 90%) to the sequence from position 87 to position 128 in SEQ ID NO: 1, as compared to the sequence identity of the CHAP domain of the invention to the sequence from position 72 to position 215 in SEQ ID NO: 1 (which may be in this example, e.g., about 60% to 80%). Hence, the present invention further relates to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a cysteine, histidine-dependent amidohydrolase / peptidase (CHAP) domain that has (i) a sequence identity of at least 60% to the sequence from position 72 to position 215 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions as compared to the sequence from position 72 to position 215 in SEQ ID NO: 1, and wherein (a) a corresponding segment of said CHAP domain has a sequency identity of at least 80%, preferably at least 90%, to the sequence from position 87 to position 128 in SEQ ID NO: 1, and / or (b) said CHAP domain has at most six, five, four, three or two, preferably at most one, more preferably no amino acid substitutions or deletions at positions 80, 87, 88, 98, 99, 103, 106, 110, 114, 122, 126, 128, 137, 182, 202, and 208 of SEQ ID NO: 1 or at positions corresponding to these positions. Preferably, said CHAP domain comprises at least one aglycosylation mutation at position 73 in SEQ ID NO: 1 or at a position corresponding to this position as described herein, preferably the substitution N73G, and / or at least one amino acid substitution described herein in context of the L0482ag variants obtained upon directed evolution, preferably at least one of the most beneficial mutations, as described herein, i.e., at least amino acid substitution selected from the group consisting of: T82S, N85G, R86K, S130N, H136K / R, F155Y, D169N, N185Y and N186G in SEQ ID NO: 1. Additional cell wall binding domain(s) Preferably, herein and in context of the present invention, the peptidoglycan hydrolase of the invention comprises, in addition to the CHAP domain of the invention, at least one cell wall binding domain. As mentioned above, endolysins often have at least one cell wall-binding domain (CBD) which recognize and bind to certain epitopes in the cell wall of the host bacterium for proper fixation of the catalytic effect of an enzymatically active domain (EAD). Normally, CBDs are enzymatically inactive by themselves. Thus, a domain which has catalytic activity and is able to recognize and bind to certain epitopes in the cell wall of a bacterium is rather considered herein as a an enzymatically active domain (EAD). Preferably, herein and in context of the present invention, the cell wall binding domain is a peptidoglycan binding domain which binds, in particular, to the peptidoglycan structure of a target bacterium. Suitable cell wall binding domains to be used in context of the present invention, include, inter alia: a LYSM domain, a SH3 domain and a choline binding domain. Preferably, in context of the present invention, the at least one cell wall binding domain comprises a LYSM domain and / or a SH3 domain, more preferably, a LYSM domain, as described herein. Preferably, herein and in context of the present invention, the cell wall binding domain is derived from an endolysin, in particular a cell wall binding domain thereof. Preferably, said endolysin has a killing activity against a Staphylococcus species or strain, more preferably against Staphylococcus aureus. In context of the present invention, the cell wall binding domain is, preferably, derived from an endolysin comprising a LYSM domain or a SH3 domain, more preferably an endolysin comprising a LYSM domain. Preferably, the LYSM domain is derived from an endolysin comprising a LYSM domain and a CHAP domain, wherein the LYSM domain is, preferably, N-terminally of the CHAP domain. In other words, the LYSM domain of the invention is, preferably, derived from an endolysin having a LYSM-CHAP architecture, as described herein, e.g. L0482 (SEQ ID NO: 1) or L0499 (SEQ ID NO: 47). Hence, in preferred embodiments, the peptidoglycan of the invention comprises, in addition, to the CHAP domain of the invention, a LYSM domain, as described herein. Preferably, in context of the invention, the cell wall binding domain, e.g. the LYSM domain, is N-terminally of the CHAP domain. Preferably herein, the LYSM domain according to the invention is defined by the sequence from position 1 to position 51 in SEQ ID NO: 1 or it has a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO: 1. In other words, the LYSM domain according to the invention is, preferably, defined by the sequence of SEQ ID NO: 302 or has a sequence identity of at least 60% to the sequence of SEQ ID NO: 302. In some embodiments, the LYSM domain is defined by the sequence from position 1 to position 47 in SEQ ID NO: 47 or it has a sequence identity of at least 60% to the sequence from position X to position Y in SEQ ID NO: 47. In some embodiments, the SH3 domain is defined by the sequence of SEQ ID NO: 376 or has a sequence identity of at least 60% to the sequence of SEQ ID NO: 376. In some embodiments, the SH3 domain is defined by the sequence of SEQ ID NO: 377 or has a sequence identity of at least 60% to the sequence of SEQ ID NO: 377. Furthermore, the cell wall binding domain of the invention, e.g. the LYSM domain of the invention, has, preferably, the ability to bind to the cell wall of a Staphylococcus species or strain, more preferably to Staphylococcus aureus, as described herein. Beneficial and permissive amino acid substitutions in the LYSM domain found by directed evolution or in silico deimmunization screens As described herein and as illustrated in the appended Example, the inventors found a variety of amino acid substitutions which were contained in the LYSM domain of L0482ag variants obtained by directed evolution; see, e.g., Table 3, the column “beneficial / permissive residues”. Of note, the L0482ag variants containing these amino acid substitutions were all well secreted from eukaryotic cells and determined to be active by the YODA method. Furthermore, as also described herein and as illustrated in the appended Examples, the inventors found deimmunizing substitutions in the LYSM domain of L0482 variants which may decrease the immunogenicity of the LYSM domain of the invention and peptidoglycan hydrolases containing the LYSM domain of the invention; see, e.g., Table 5, column “deimm”. Thus, the LYSM domain of the invention (which preferably has a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO: 1) may have one or more amino acid substitutions at positions 1 to 6, 8, 10 to 13, 16 to 20, 22 to 30, 32 to 45 and 47 to 51 in SEQ ID NO: 1 or at positions corresponding to these positions, preferably, wherein the amino acid residue at position 1 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tryptophan, glutamine or asparagine, the amino acid residue at position 2 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 3 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 4 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 5 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 6 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine or proline, the amino acid residue at position 8 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 10 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine or alanine, the amino acid residue at position 11 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or isoleucine, the amino acid residue at position 12 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glycine, glutamine or serine, the amino acid residue at position 13 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, aspartic acid, asparagine, proline or arginine, the amino acid residue at position 16 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with methionine, the amino acid residue at position 17 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, isoleucine, methionine or phenylalanine, the amino acid residue at position 18 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine or proline, the amino acid residue at position 19 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, histidine, lysine, asparagine, glutamine, serine or valine, the amino acid residue at position 20 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with methionine or valine, the amino acid residue at position 22 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, aspartic acid, glycine, histidine, lysine, glutamine, arginine or tryptophan, the amino acid residue at position 23 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, asparagine, glutamine or tryptophan, the amino acid residue at position 24 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine, histidine, threonine or asparagine, the amino acid residue at position 25 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, aspartic acid, glycine, histidine, glutamine, serine or arginine, the amino acid residue at position 26 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 27 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 28 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, glutamine, serine, threonine or alanine, the amino acid residue at position 29 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 30 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, alanine, glutamic acid, glutamine or serine, the amino acid residue at position 32 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, lysine, methionine or arginine, the amino acid residue at position 33 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, alanine, glutamic acid, glycine, lysine, glutamine or serine, the amino acid residue at position 34 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, tryptophan or isoleucine, the amino acid residue at position 36 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glycine, glutamine isoleucine or serine, the amino acid residue at position 37 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, aspartic acid, lysine, methionine, asparagine, glutamine or valine, the amino acid residue at position 38 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, serine or glycine, the amino acid residue at position 39 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, alanine, aspartic acid, glycine or isoleucine, the amino acid residue at position 40 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, aspatic acid, glycine, asparagine, serine, leucine or glutamine, the amino acid residue at position 41 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, aspartic acid or threonine, the amino acid residue at position 42 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, histidine, lysine, methionine, asparagine, glutamine or serine, the amino acid residue at position 43 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, valine or threonine, the amino acid residue at position 44 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, histidine, serine, tryptophan, or leucine. the amino acid residue at position 45 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, aspartic acid, glutamic acid, lysine, proline, glutamine or threonine, the amino acid residue at position 47 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 48 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, asparagine, glutamine, isoleucine or arginine, the amino acid residue at position 49 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, methionine or asparagine, the amino acid residue at position 50 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, histidine, asparagine, threonine or isoleucine, and / or the amino acid residue at position 51 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine. The above amino acid substitutions may be considered as beneficial or, at least, permissive for the desired pharmaceutical properties of the peptidoglycan hydrolases of the invention, as described herein, e.g., as described in context of beneficial or permissive amino acid substitutions in the CHAP domain. Furthermore, the LYSM domain of the invention (which preferably has a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO: 1) may have one or more amino acid substitutions at positions 1, 8, 10, 12, 13, 17, 19, 22 to 25, 28 to 30, 32 to 45 and 48 to 51 in SEQ ID NO: 1 or at positions corresponding to these positions, preferably, wherein the amino acid residue at position 1 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tryptophan or glutamine, the amino acid residue at position 8 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 10 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 12 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glycine, glutamine or serine, the amino acid residue at position 13 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, aspartic acid, asparagine or proline, the amino acid residue at position 17 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, isoleucine or methionine, the amino acid residue at position 19 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, histidine, lysine, asparagine or glutamine, the amino acid residue at position 22 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, aspartic acid, glycine, histidine, lysine, glutamine, arginine or tryptophan, the amino acid residue at position 23 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, asparagine, glutamine or tryptophan, the amino acid residue at position 24 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine, histidine or threonine, the amino acid residue at position 25 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, aspartic acid, glycine, histidine, glutamine or serine, the amino acid residue at position 28 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, glutamine, serine or threonine, the amino acid residue at position 29 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 30 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, alanine, glutamic acid or glutamine, the amino acid residue at position 32 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, lysine or methionine, the amino acid residue at position 33 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, alanine, glutamic acid, glycine, lysine or glutamine, the amino acid residue at position 34 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or tryptophan, the amino acid residue at position 36 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glycine or glutamine, the amino acid residue at position 37 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, aspartic acid, lysine, methionine, asparagine or glutamine, the amino acid residue at position 38 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or serine, the amino acid residue at position 39 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, alanine, aspartic acid or glycine, the amino acid residue at position 40 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, aspartic acid, glycine, asparagine, or serine, the amino acid residue at position 41 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or aspartic acid, the amino acid residue at position 42 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, histidine, lysine, methionine, asparagine, glutamine or serine, the amino acid residue at position 43 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine or valine, the amino acid residue at position 44 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, histidine, serine or tryptophan, the amino acid residue at position 45 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, aspartic acid, glutamic acid, lysine, proline, glutamine or threonine, the amino acid residue at position 48 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, asparagine or glutamine, the amino acid residue at position 49 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, methionine or asparagine, the amino acid residue at position 50 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, histidine, asparagine or threonine, and / or the amino acid residue at position 51 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine. The above amino acid substitutions may be considered as beneficial or, at least, permissive for the desired pharmaceutical properties of the peptidoglycan hydrolases of the invention, as described herein. As already mentioned above, e.g. in context of the CHAP domain of the invention, Table 3 shows positions in SEQ ID NO: 1 where beneficial or permissive amino acid substitutions have been found. These are the positions for which the column “beneficial / permissive residues” in Table 3 shows at least one amino acid residue, regardless of whether said residue is shown without parentheses or in parentheses. These positions are also called “permissive positions” herein. Furthermore, positions 1 to 51 in Table 3 for which the column “beneficial / permissive residues” shows at least one amino acid residue, regardless of whether said residue is shown without parentheses or in parentheses are considered as “permissive positions” in the LYSM domain herein. As already mentioned above, herein and in context of the present invention, an amino acid residue in SEQ ID NO: 1 corresponding to a beneficial or permissive position may be substituted with an amino acid residue shown in the column “beneficial / permissive residues” in Table 3 for said position, i.e. a residue shown without parentheses or in parentheses in said column in Table 3, preferably with a residue that is shown without parentheses in said column in Table 3. Thus, in some embodiments, in particular in context of permissive / beneficial mutations and Table 3, the LYSM domain has at least one amino acid substitution at the permissive positions in the LSYM domain or at positions corresponding to said permissive positions in the LYSM domain. Preferably, in these embodiments, at least one amino acid residue at said permissive positions in the LSYM domain or at positions corresponding to said permissive positions in the LYSM domain is substituted with an amino acid residue shown in the column “beneficial / permissive residues” in Table 3 for said positions, more preferably with a residue that is shown without parentheses in said column in Table 3. Particularly beneficial amino acid substitutions in the LYSM domain Furthermore, as described herein, the inventors found hits variants, i.e. G1 to G4, H1 to H10 and I1 to I30, which contained certain amino acid substitutions in the LYSM domain; see, e.g., Table 4. These amino acid substitutions are thus considered in context of the invention as particularly beneficial mutations, i.e., amino acid substitutions, in the LYSM domain. As described herein, e.g., in context of the CHAP domain of the invention, “particularly beneficial amino acid substitutions” may be particularly beneficial for maintaining or enhancing the desired pharmaceutical properties of peptidoglycan hydrolases, in particular, the bactericidal activity (e.g., against S. aureus), the stability and / or the ability of being secreted from eukaryotic cells, e.g. human cells. This is also true for the particularly beneficial amino acid substitutions in the LYSM domain. Hence, the LYSM domain of the invention (which preferably has a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO: 1), has, preferably, one or more amino acid substitutions at positions 1, 8, 10, 13, 23 to 25, 30, 33, 37, and 39 to 41 in SEQ ID NO: 1 or at positions corresponding to these positions, preferably, wherein the amino acid residue at position 1 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tryptophan, the amino acid residue at position 8 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 10 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 13 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 23 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 24 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine, the amino acid residue at position 25 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 30 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 33 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 37 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 39 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 40 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, and / or the amino acid residue at position 41 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine. As mentioned above, the cell wall binding domain of the invention, e.g. the LYSM domain of the invention, has, preferably, the ability to bind to the cell wall of a Staphylococcus species or strain, more preferably to Staphylococcus aureus. Furthermore, a peptidoglycan hydrolase comprising a CHAP domain and / or a LYSM domain as described herein has, preferably, a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, as described herein. Additional linker Preferably, herein and in context of the present invention, in particular in context of peptidoglycan hydrolase comprising a CHAP domain and a CBD, the peptidoglycan hydrolase comprises a peptide linker between the CHAP domain and the cell wall binding domain. The peptide linker is not limited to any specific linkers and any linkers used in the art for connecting different domains or parts of proteins such as fusion proteins may be used herein and in context of the present invention. As used herein, the term "peptide linker" refers to a peptide or polypeptide sequence which connects two or more domains (e.g., the CHAP domain or the invention and a cell wall binding domain, and / or the CHAP of the invention and an extended pharmacokinetic (PK) peptide) in a linear amino acid sequence of a polypeptide chain. Preferably, the linker is a flexible linker. Exemplary linkers include glycine-serine-polypeptide linkers, glycine-proline- polypeptide linkers, and proline-alanine polypeptide linkers. An exemplary linker with a furin cleavage site (which may be also used in context of the present invention) is shown in SEQ ID NO: 370. In some embodiments, the linker is a glycine-serine linker, i.e., a peptide that predominantly, essentially or exclusively consists of glycine and serine residues. Herein and in context of the present invention, a glycine-serine linker may comprise, for example, one or multiple copies (e.g.2 to 5 copies) of the sequence shown in SEQ ID NO: 297 (i.e. GGGGS). Preferably, said copies are directly adjacent to each other, for example, as shown in SEQ ID NO: 298 or 299 (i.e. GGGGSGGGGS (GS2: 2x GGGGS), or GGGGSGGGGSGGGGSGGGGS (GS4: 4x GGGGS), respectively. Moreover, GS3 (3x GGGGS) or G5 (5x GGGGS) may be equally used. Further suitable glycine-serine linkers are shown in SEQ ID NO: 363 to 369. Another suitable glycine-serine linker has the sequence “GGS”. In certain embodiments, the peptide linker is derived from an endolysin, in particular, a linker sequence thereof. Preferably, said endolysin has a killing activity against a Staphylococcus species or strain, preferably Staphylococcus aureus. In some preferred embodiments, the peptide linker is a L0482-derived linker, i.e. a linker which has a sequence identity of at least 60% to the sequence from position 52 to position 71 in SEQ ID NO: 1. Beneficial and permissive amino acid substitutions in the L0482 linker found by aglycosylation screen, directed evolution, or in silico deimmunization screen As described herein and as illustrated in the appended Examples, the inventors found a variety of amino acid substitutions which were contained in the linker sequence of L0482 variants obtained by directed evolution; see, e.g., Table 3, the column “beneficial / permissive residues”. Of note, the L0482 variants containing these amino acid substitutions were all well secreted from eukaryotic cells and determined to be active by the YODA method. Furthermore, as also described herein and as illustrated in the appended Examples, the inventors found deimmunizing substitutions in the linker sequence of L0482 variants which may decrease the immunogenicity of the linker sequence and peptidoglycan hydrolases containing such a linker; see, e.g., Table 5, column “deimm”. Furthermore, the inventors found amino acid substitutions at position 68 in SEQ ID NO: 1, i.e. aglycosylation substitutions in the linker of L0482, which enhance the bactericidal activity upon expression in eukaryotic cells, as described herein; see, e.g., Example 4. Thus, the L0482-derived linker (which may have a sequence identity of at least 60% to the sequence from position 52 to position 71 in SEQ ID NO: 1), may have one or more amino acid substitutions at positions 52 to 56, 58, 60 to 66, and 68, to 71 in SEQ ID NO: 1 or at positions corresponding to these positions, preferably wherein the amino acid residue at position 52 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 53 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, alanine, glycine, lysine, glutamine or serine, the amino acid residue at position 54 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, histidine. asparagine, alanine or isoleucine, the amino acid residue at position 55 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, aspartic acid or serine, the amino acid residue at position 56 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or isoleucine, the amino acid residue at position 58 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 60 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or isoleucine, the amino acid residue at position 61 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine or glutamine, the amino acid residue at position 62 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid or asparagine, the amino acid residue at position 63 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, alanine or methionine, the amino acid residue at position 64 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine or leucine, the amino acid residue at position 65 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, aspartic acid, asparagine or arginine, the amino acid residue at position 66 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with , lysine, methionine, arginine, alanine or serine, the amino acid residue at position 69 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, histidine, asparagine or glutamine, the amino acid residue at position 70 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, and / or the amino acid residue at position 71 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine or aspartic acid. The above amino acid substitutions may be considered as beneficial or, at least, permissive for the desired pharmaceutical properties of the peptidoglycan hydrolases of the invention, as described herein, e.g., as described in context of beneficial or permissive amino acid substitutions in the CHAP domain. Furthermore, the peptide linker (which may have a sequence identity of at least 60% to the sequence from position 52 to position 71 in SEQ ID NO: 1) may have one or more amino acid substitutions at positions 52 to 56, 58, 63, 65, 68, 69 and 71 in SEQ ID NO: 1 or at positions corresponding to these positions, preferably wherein the amino acid residue at position 52 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 53 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, alanine, glycine, lysine, glutamine or serine, the amino acid residue at position 54 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, glutamic acid, histidine or asparagine, the amino acid residue at position 55 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine or aspartic acid, the amino acid residue at position 56 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 58 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 63 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, the amino acid residue at position 65 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine or aspartic acid, the amino acid residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, methionine, arginine, alanine or serine, the amino acid residue at position 69 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, histidine, asparagine or glutamine, and / or the amino acid residue at position 71 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine. The above amino acid substitutions may be considered as beneficial or, at least, permissive for the desired pharmaceutical properties of the peptidoglycan hydrolases of the invention, as described herein. As already mentioned above, e.g. in context of the CHAP domain of the invention, Table 3 shows positions in SEQ ID NO: 1 where beneficial or permissive amino acid substitutions have been found. These are the positions for which the column “beneficial / permissive residues” in Table 3 shows at least one amino acid residue, regardless of whether said residue is shown without parentheses or in parentheses. These positions are also called “permissive positions” herein. Furthermore, positions 52 to 71 in Table 3 for which the column “beneficial / permissive residues” shows at least one amino acid residue, regardless of whether said residue is shown without parentheses or in parentheses are considered as “permissive positions” in the linker of L0482 herein. Herein and in context of the present invention, an amino acid residue in SEQ ID NO: 1 corresponding to a beneficial or permissive position may be substituted with an amino acid residue shown in the column “beneficial / permissive residues” in Table 3 for said position, i.e. a residue shown without parentheses or in parentheses in said column in Table 3, preferably with a residue that is shown without parentheses in said column in Table 3. In some embodiments, in particular in context of permissive / beneficial mutations and Table 3, the L0482-derived peptide linker has at least one amino acid substitution at the permissive positions in the linker region of L0482 or at positions corresponding to said permissive positions in the linker region of L0482. Preferably, in these embodiments, at least one amino acid residue at said permissive positions the linker region of L0482 or at positions corresponding to said permissive positions in the linker region of L0482 is substituted with an amino acid residue shown in the column “beneficial / permissive residues” in Table 3 for said positions, more preferably with a residue that is shown without parentheses in said column in Table 3. Particularly beneficial amino acid substitutions in the L0482 linker Furthermore, as described herein, the inventors found hits variants, i.e. G1 to G4, H1 to H10 and I1 to I30, which contained certain amino acid substitutions in the linker region of L0482 variants; see, e.g., Table 4. These amino acid substitutions are thus considered in context of the invention as particularly beneficial mutations, i.e., amino acid substitutions, in the L0482-derived peptide linker. As described herein, e.g., in context of the CHAP domain of the invention, “particularly beneficial amino acid substitutions” may be particularly beneficial for maintaining or enhancing the desired pharmaceutical properties of peptidoglycan hydrolases, in particular, the bactericidal activity (e.g., against S. aureus), the stability and / or the ability of being secreted from eukaryotic cells, e.g. human cells. This is also true for the particularly beneficial amino acid substitutions in the linker of L0482. Thus, in some preferred embodiments, in particular in context of L0482-derived peptide linkers, the peptide linker has a sequence identity of at least 60% to the sequence from position 52 to position 71 in SEQ ID NO: 1, and has one or more amino acid substitutions at positions 53, 55, 56, 58, 63, 65 and 68 in SEQ ID NO: 1 or at positions corresponding to these positions, preferably wherein the amino acid residue at position 53 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, the amino acid residue at position 55 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, the amino acid residue at position 56 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 58 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 63 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, the amino acid residue at position 65 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, and / or the amino acid residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine. Preferably, said peptide linker has an aglycosylation mutation, e.g., a deletion (preferably and amino acid substitution) at position 68 in SEQ ID NO: 1 or at a position corresponding to this position, as described herein. Preferably, the L0482-derived peptide linker has an amino acid substitution at position 68 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid residue at said position is substituted with lysine, methionine, arginine or alanine, preferably lysine. Furthermore, said peptide linker has (in addition to said aglycosylation mutation), preferably, at least one amino acid substitution at positions 53, 55, 56, 58, 63 and 65 in SEQ ID NO: 1 or at positions corresponding to these positions, as described herein, e.g., as just described above. Furthermore, a peptidoglycan hydrolase comprising a CHAP domain, a LYSM domain and / or an L0482-derived peptide linker, as described herein, has, preferably, a sequence identity of at least 60% to the sequence of SEQ ID NO: 1, as described herein. LYSM domain of the invention and peptidoglycan hydrolases comprising a LYSM domain of the invention As described herein and as illustrated in the appended Examples, the inventors found particularly beneficial amino acid substitutions in the LYSM domain of L0482. Thus, the present invention relates, in some aspects, to a LYSM domain that has (i) a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions at positions 1, 8, 10, 13, 23 to 25, 30, 33, 37, and 39 to 41 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 1 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tryptophan, the amino acid residue at position 8 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 10 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 13 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 23 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 24 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine, the amino acid residue at position 25 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 30 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 33 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 37 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 39 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 40 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, and / or the amino acid residue at position 41 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine. In particular, said LYSM domain has the ability to bind to the cell wall of a Staphylococcus species or strain, more preferably to Staphylococcus aureus, as described herein. Moreover, said LYSM domain is particularly advantageous for use in a peptidoglycan hydrolase having bactericidal activity, as described herein and in context of the present invention. Thus, the present invention further relates, e.g. in context of the LYSM domain of the invention, to a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises (a) an enzymatically active domain and (b) a LYSM domain that has (i) a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions at positions 1, 8, 10, 13, 23 to 25, 30, 33, 37, and 39 to 41 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 1 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tryptophan, the amino acid residue at position 8 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, t...

Claims

Claims 1. A peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a cysteine, histidine-dependent amidohydrolase / peptidase (CHAP) domain that has (i) a sequence identity of at least 83% to the sequence from position 72 to position 215 in SEQ ID NO: 1; (ii) an amino acid substitution or a deletion at position 73 in SEQ ID NO: 1 or at a position corresponding to this position; and (iii) one or more amino acid substitutions at positions 86, 82, 85, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine.

2. The peptidoglycan hydrolase of claim 1 which has a sequence identity of at least 60% to the sequence of SEQ ID NO:

1.

3. The peptidoglycan hydrolase of claim 2 which further comprises an amino acid substitution or a deletion at position 68 in SEQ ID NO: 1 or at a position corresponding to this position, preferably wherein the amino acid residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, methionine, arginine or alanine, more preferably with lysine 4. The peptidoglycan hydrolase of any one of claims 1 to 3, wherein the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, preferably with glycine.

5. The peptidoglycan hydrolase of any one of claims 1 to 4, wherein said CHAP domain has at least one, preferably at least two or more, of the following consensus mutation units I) to V): I) an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; II) an amino acid substitution pair at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, and the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; III) an amino acid substitution pair at positions 130 and 136 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, and the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine; IV) an amino acid substitution at position 169 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine; and / or V) an amino acid substitution pair at positions 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine.

6. The peptidoglycan hydrolase of claim 5, wherein the CHAP domain further has an amino acid substitution at position 155 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the phenylalanine at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine.

7. The peptidoglycan hydrolase of any one of claims 1 to 6, wherein said CHAP domain has an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine.

8. The peptidoglycan hydrolase of any one of claims 1 to 7, wherein said CHAP domain has a sequence identity of at least 94% to the sequence from position 72 to position 215 in SEQ ID NO:

11.

9. The peptidoglycan hydrolase of any one of claims 1 to 7, wherein said CHAP domain has (a) an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine;(b) at least one, preferably two, amino acid substitution(s) at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, and the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; and / or (c) an amino acid substitution at position 169 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine.

10. The peptidoglycan hydrolase of claim 9, wherein the CHAP domain further comprises one or more amino acid substitutions at positions 173, 175 and 192 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, and / or the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine.

11. The peptidoglycan hydrolase of any one of claims 1 to 10 further comprising at least one cell wall binding domain, preferably at least one cell wall binding domain derived from an endolysin, more preferably a LYSM domain and / or a SH3 domain.

12. The peptidoglycan hydrolase of any one of claims 1 to 11 comprising a LYSM domain that has a sequence identity of at least 60% to the sequence from position 1 to position 51 in SEQ ID NO:

1.

13. The peptidoglycan hydrolase of claim 12, wherein the LYSM domain has one or more amino acid substitutions at positions 1, 8, 10, 13, 23 to 25, 30, 33, 37, and 39 to 41 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 1 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tryptophan, the amino acid residue at position 8 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 10 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine, the amino acid residue at position 13 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 23 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine,the amino acid residue at position 24 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with cysteine, the amino acid residue at position 25 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 30 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 33 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with aspartic acid, the amino acid residue at position 37 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 39 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 40 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with threonine, and / or the amino acid residue at position 41 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine.

14. The peptidoglycan hydrolase of any one of claims 1 to 13 which has a killing activity against at least one Staphylococcus species or strain, preferably against Staphylococcus aureus, more preferably against a Staphylococcus aureus strain that is resistant to at least one antibiotic such as methicillin.

15. The peptidoglycan hydrolase of claim 14, wherein said Staphylococcus species or strain, preferably said Staphylococcus aureus, is present in form of a biofilm or is suspected of forming a biofilm.

16. The peptidoglycan hydrolase of any one of claims 1 to 15 which is stable up to a temperature of about 40°C.

17. The peptidoglycan hydrolase of any one of claims 1 to 16, which has, compared to the peptidoglycan hydrolase of SEQ ID NO: 1, an enhanced killing activity against Staphylococcus aureus, an enhanced ability of being secreted by a human cell, and / or an enhanced thermostability.

18. The peptidoglycan hydrolase of any one of claims 1 to 17 further comprising an extended pharmacokinetic (PK) peptide such as a human FC domain, a C-terminal peptide of human chorionic gonadotropin or human lysozyme.

19. The peptidoglycan hydrolase of any one of claims 1 to 18 further comprising a signal peptide, preferably at the N-terminus.

20. A nucleic acid encoding the peptidoglycan hydrolase of any one of claims 1 to 19.

21. The nucleic acid of claim 20, wherein said peptidoglycan hydrolase comprises a signal peptide, preferably at the N-terminus.

22. The nucleic acid of claim 20 or 21 which is an RNA.

23. The nucleic acid of any one of claims 20 to 22 which is an RNA construct comprising in 5' to 3' order: (i) a 5' UTR that comprises or consists of a modified human alpha-globin 5'-UTR; (ii) a sequence encoding a peptidoglycan hydrolase of any one of claims 1 to 19; (iii) a 3' UTR that comprises or consists of a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA; and (iv) a poly-A sequence; and, preferably, wherein said RNA construct further comprises (v) a 5' cap and / or (vi) a modified nucleoside selected from pseudouridine (ψ), N1-methyl-pseudouridine (m1ψ), and 5- methyl-uridine (m5U), preferably N1-methyl-pseudouridine (m1ψ), in place of uridine, preferably in place of each uridine.

24. A pharmaceutical composition comprising the peptidoglycan hydrolase of any one of claims 1 to 19 and / or the nucleic acid of any one of claims 20 to 23; and, preferably, a pharmaceutically acceptable excipient.

25. The peptidoglycan hydrolase of any one of claims 1 to 19, the nucleic acid of any one of claims 20 to 23 or the pharmaceutical composition of claim 24 for use in treating a disease caused by and / or associated with a Staphylococcus infection and / or a subject that has or is suspected of having a Staphylococcus infection.

26. The peptidoglycan hydrolase, nucleic acid or pharmaceutical composition for use according to claim 25, wherein said infection is a Staphylococcus aureus infection.

27. A pharmaceutical composition comprising a peptidoglycan hydrolase having bactericidal activity, wherein the peptidoglycan hydrolase comprises a cysteine, histidine-dependent amidohydrolase / peptidase (CHAP) domain that has (i) a sequence identity of at least 60% to the amino acid sequence from position 72 to position 215 in SEQ ID NO: 1; and that has (ii) one or more amino acid substitutions as compared to the amino acid sequence from position 72 to position 215 in SEQ ID NO: 1; and, preferably, wherein said pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

28. The pharmaceutical composition of claim 27, wherein said CHAP domain has an amino acid substitution or a deletion at position 73 in SEQ ID NO: 1 or at a position corresponding to this position, preferably, wherein the residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, tyrosine, leucine, glutamic acid, alanine, histidine or serine, more preferably with glycine.

29. The pharmaceutical composition of claim 27 or 28, wherein said peptidoglycan hydrolase has a sequence identity of at least 60% to the sequence of SEQ ID NO:

1.

30. The pharmaceutical composition of claim 29, wherein said peptidoglycan hydrolase further comprises an amino acid substitution or a deletion at position 68 in SEQ ID NO: 1 or at a position corresponding to this position, preferably, wherein the amino acid residue at position 68 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, methionine, arginine or alanine, more preferably with lysine.

31. The pharmaceutical composition of any one of claims 27 to 30, wherein said CHAP domain has one or more amino acid substitutions at positions 73, 75, 78, 81, 82, 85, 86, 104, 107, 115, 124, 125, 130, 133, 135, 136, 140, 141, 155, 169, 173, 175, 178, 185, 186, 191, 192, 194, 198, 204, 212 and 215 in SEQ ID NO: 1 or at positions corresponding to these positions, and wherein the amino acid residue at position 73 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine or serine, the amino acid residue at position 75 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 78 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 81 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamic acid, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 104 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine, the amino acid residue at position 107 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 115 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 124 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with phenylalanine, the amino acid residue at position 125 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with valine,the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 133 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 135 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with histidine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, the amino acid residue at position 140 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 141 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 173 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 175 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 178 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with leucine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 191 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with arginine, the amino acid residue at position 192 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glutamine, the amino acid residue at position 194 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with alanine, the amino acid residue at position 198 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with isoleucine,the amino acid residue at position 204 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 212 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue at position 215 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine.

32. The pharmaceutical composition of any one of claims 27 to 31, wherein said CHAP domain has one or more amino acid substitutions at positions 86, 82, 85, 130, 136, 155, 169, 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, and wherein the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine, the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine, the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine, preferably with lysine, the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, the amino acid residue at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and / or the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine.

33. The pharmaceutical composition of any one of claims 27 to 32, wherein said CHAP domain has an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, preferably wherein the amino acid residue at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine.

34. The pharmaceutical composition of any one of claims 27 to 33, wherein said CHAP domain has at least one, preferably at least two or more, of the following consensus mutation units I) to V):I) an amino acid substitution at position 86 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 86 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine; II) an amino acid substitution pair at positions 82 and 85 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 82 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with serine, and the amino acid residue at position 85 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine; III) an amino acid substitution pair at positions 130 and 136 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 130 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine, and the amino acid residue at position 136 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with lysine or arginine; IV) an amino acid substitution at position 169 in SEQ ID NO: 1 or at a position corresponding to this position, wherein the amino acid at position 169 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with asparagine; and / or V) an amino acid substitution pair at positions 185 and 186 in SEQ ID NO: 1 or at positions corresponding to these positions, wherein the amino acid residue at position 185 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine, and the amino acid residue at position 186 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with glycine.

35. The pharmaceutical composition of any one of claims 27 to 34, wherein said CHAP domain has an amino acid substitution at position 155 in SEQ ID NO: 1 or at a position corresponding to this position, preferably wherein the amino acid residue at position 155 in SEQ ID NO: 1 or at a position corresponding to this position is substituted with tyrosine.

36. The pharmaceutical composition of any one of claims 27 to 35, wherein (i) a corresponding segment of said CHAP domain has a sequency identity of at least 80%, preferably at least 90%, to the sequence from position 87 to position 128 in SEQ ID NO: 1, and / or (ii) said CHAP domain has at most six, five, four, three or two, preferably at most one, more preferably no amino acid substitutions or deletions at positions 80, 87, 88, 98, 99, 103, 106, 110, 114, 122, 126, 128, 137, 182, 202, and 208 of SEQ ID NO: 1 or at positions corresponding to these positions.

37. The pharmaceutical composition of any one of claims 27 to 36, wherein said peptidoglycan hydrolase further comprises at least one cell wall binding domain as defined in claim 11, preferably a LYSM domain as defined in claim 12 or 13.

38. The pharmaceutical composition of any one of claims 27 to 37, wherein said peptidoglycan hydrolase has a killing activity against at least one Staphylococcus species or strain, preferably against Staphylococcus aureus, more preferably against a Staphylococcus aureus strain that is resistant to at least one antibiotic such as methicillin.

39. The pharmaceutical composition of claim 38, wherein said Staphylococcus species or strain, preferably said Staphylococcus aureus, is present in form of a biofilm or is suspected of forming a biofilm.

40. The pharmaceutical composition of any one of claims 27 to 39, wherein the peptidoglycan hydrolase is stable up to a temperature of about 40°C.

41. The pharmaceutical composition of any one of claims 27 to 40, wherein the peptidoglycan hydrolase has, compared to the peptidoglycan hydrolase of SEQ ID NO: 1, an enhanced killing activity against Staphylococcus aureus, an enhanced ability of being secreted by a human cell, and / or an enhanced thermostability.

42. The pharmaceutical composition of any one of claims 27 to 41, wherein said CHAP domain has a sequence identity of at least 80% to the amino acid sequence from position 72 to position 215 in SEQ ID NO:

1.

43. The pharmaceutical composition of any one of claims 27 to 42, wherein said CHAP domain has a sequence identity of at least 90% to the amino acid sequence from position 72 to position 215 in SEQ ID NO:

1.

44. The pharmaceutical composition of any one of claims 27 to 43, wherein said CHAP domain has a sequence identity of at least 94% to the sequence from position 72 to position 215 in SEQ ID NO:

11.

45. The pharmaceutical composition of any one of claims 27 to 44, wherein the peptidoglycan hydrolase further comprises an extended pharmacokinetic (PK) peptide such as a human FC domain, a C-terminal peptide of human chorionic gonadotropin or human lysozyme.

46. The pharmaceutical composition of any one of claims 27 to 45, wherein the peptidoglycan hydrolase further comprises a signal peptide, preferably at the N-terminus.

47. A pharmaceutical composition comprising a nucleic acid encoding a peptidoglycan hydrolase as defined in any one of claims 27 to 46.

48. The pharmaceutical composition of claim 47, wherein the peptidoglycan hydrolase comprises a signal peptide, preferably at the N-terminus.

49. The pharmaceutical composition of claim 47 or 48, wherein said nucleic acid is an RNA.

50. The pharmaceutical composition of any one of claims 47 to 49, wherein said nucleic acid is an RNA construct comprising in 5' to 3' order: (i) a 5' UTR that comprises or consists of a modified human alpha-globin 5'-UTR; (ii) a sequence encoding a peptidoglycan hydrolase as defined in any one of claims 25 to 45; (iii) a 3' UTR that comprises or consists of a first sequence from the amino terminal enhancer of split (AES) messenger RNA and a second sequence from the mitochondrial encoded 12S ribosomal RNA; and (iv) a poly-A sequence; and, preferably, wherein said RNA construct further comprises(v) a 5' cap and / or (vi) a modified nucleoside selected from pseudouridine (ψ), N1-methyl-pseudouridine (m1ψ), and 5- methyl-uridine (m5U), preferably N1-methyl-pseudouridine (m1ψ), in place of uridine, preferably in place of each uridine.

51. The pharmaceutical composition of any one of claims 27 to 50 for use in treating a disease caused by and / or associated with a Staphylococcus infection and / or a subject that has or is suspected of having a Staphylococcus infection.

52. The pharmaceutical composition for use according to claim 51, wherein said infection is a Staphylococcus aureus infection.

53. The peptidoglycan hydrolase, nucleic acid or pharmaceutical composition for use according to claim 25 or 26 or the pharmaceutical composition for use according to claim 51 or 52, wherein the Staphylococcus is present in form of a biofilm and / or a free-floating aggregate, or is suspected of forming a biofilm and / or a free-floating aggregate.

54. The peptidoglycan hydrolase, nucleic acid or pharmaceutical composition for use according to any one of claims 25, 26 and 53 or the pharmaceutical composition for use according to any one of claims 51 to 53, wherein said Staphylococcus infection is a Staphylococcus aureus infection of a skin, soft tissue, bone, lung, sinus and / or urinary tract.

55. The peptidoglycan hydrolase, nucleic acid or pharmaceutical composition for use according to any one of claims 25, 26, 53 and 54 or the pharmaceutical composition for use according to any one of claims 51 to 54, wherein said disease is selected from the group consisting of: pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome, bacteremia, sepsis, a respiratory infection such as sinusitis, pimples, impetigo, boils, cellulitis, folliculitis, carbuncles, scalded skin syndrome, abscesses, food poisoning, necrotizing fasciitis, pyomyositis, mediastinitis, infected dermatitis, wound infection, diabetic foot ulcer, septic arthritis, osteoarticular infections, prosthetic infection such as infection of a prosthetic joint or a cardiac device, and urinary tract infections.

56. The peptidoglycan hydrolase, nucleic acid or pharmaceutical composition for use according to claim 55, wherein said disease is pneumonia, bacteremia, endocarditis, or a prosthetic infection.

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